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Biomedical subjects

U Pedersen-Bjergaard

Publications and source records attributed to U Pedersen-Bjergaard.

At least 19 recordsLinked to original sources

Frequency and risk factors of severe hypoglycaemia in insulin-treated Type 2 diabetes: a cross-sectional survey.

AIMS: The reported risk of severe hypoglycaemia in insulin-treated Type 2 diabetes is highly variable and few studies have evaluated the influence of risk factors. We assessed the incidence and the influence of potential risk factors for severe hypoglycaemia in a questionnaire survey in subjects with insulin-treated Type 2 diabetes receiving currently recommended multifactorial intervention. METHODS: Consecutive patients with insulin-treated Type 2 diabetes (n = 401) completed a questionnaire about occurrence of hypoglycaemia in the past, hypoglycaemia awareness and socio-demographic factors. A zero-inflated negative binomial model was used to assess the influence of potential risk factors on the rate of severe hypoglycaemia. RESULTS: The overall incidence of severe hypoglycaemia in the preceding year was 0.44 episodes/person year. Sixty-six (16.5%) patients had experienced at least one event. The risk of any episode of severe hypoglycaemia positively correlated with impaired hypoglycaemia awareness, being married and long duration of diabetes. The risk of repeated episodes of severe hypoglycaemia positively correlated with the presence of peripheral neuropathy, while long duration of diabetes prior to insulin treatment and treatment with angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor antagonists (ARBs) were associated with reduced risk. C-peptide concentration and HbA1c were not associated with the risk of severe hypoglycaemia. CONCLUSIONS: In this cohort of insulin-treated Type 2 diabetic patients, the incidence of severe hypoglycaemia is higher than reported in most studies, corresponding to about one-third of that in Type 1 diabetes. Impaired hypoglycaemia awareness is the most important risk factor for severe hypoglycaemia.

Adult↗

Association between plasma activities of semicarbazide-sensitive amine oxidase and angiotensin-converting enzyme in patients with type 1 diabetes mellitus.

AIMS/HYPOTHESIS: Plasma semicarbazide-sensitive amine oxidase (SSAO) is elevated in patients with type 1 and type 2 diabetes and has been implicated in the pathophysiology of diabetic late complications. The regulation of SSAO production remains unknown. We studied correlations between plasma SSAO activity and parameters associated with diabetic late complications. METHODS: Plasma SSAO was measured in a well-characterised group of 287 patients with type 1 diabetes. Standard statistical methods were used to investigate correlations with clinical parameters and components of the renin-angiotensin system. RESULTS: Overall, plasma SSAO was elevated, at 693+/-196 mU/l (mean+/-SD; normal controls 352+/-102 mU/l). Plasma SSAO was higher in the group with late complications or hypertension, and in patients treated with ACE-inhibitors. In univariate analysis a significant positive correlation (p<0.001, r=0.27) was found between plasma SSAO and serum ACE activity in patients untreated with ACE inhibitors or angiotensin II receptor antagonists (n=221), but plasma SSAO did not differ by ACE I/D genotype. Plasma SSAO correlated positively with duration of diabetes, HbA(1)c and plasma renin, and negatively with plasma angiotensinogen and body mass index. A multiple regression analysis including these variables resulted in serum ACE activity (p<0.001), ACE genotype (negatively, p<0.001) and HbA(1)c (p=0.023) as explaining variables. CONCLUSIONS/INTERPRETATION: Results suggest that a common factor is involved in the regulation of both plasma SSAO and serum ACE, which is different from the genetic determination of ACE activity.

Amine Oxidase (Copper-Containing)↗

Reproducibility and reliability of hypoglycaemic episodes recorded with Continuous Glucose Monitoring System (CGMS) in daily life.

AIM: Continuous glucose monitoring may reveal episodes of unrecognized hypoglycaemia. We evaluated reproducibility and reliability of hypoglycaemic episodes recorded in daily life by the Medtronic MiniMed Continuous Glucose Monitoring System (CGMS). METHODS: Twenty-nine adult patients with Type 1 diabetes underwent 6 days of continuous subcutaneous glucose monitoring, applying one CGMS on each side of the abdomen. Blood glucose was measured by HemoCue B-Glucose Analyzers six times daily and two different 4-point calibration sets were generated (set A and B). Using these calibration sets, CGMS raw data were recalibrated generating four different CGMS data sets [left-A (left side of abdomen, calibration set A), left-B, right-A and right-B]. Agreement between CGMS data sets was evaluated during hypoglycaemic events, comparing CGMS readings = 2.2 mmol/l with nadir values from corresponding CGMS data sets. CGMS readings were also compared with independent self-monitored blood glucose (SMBG) values. RESULTS: With hypoglycaemia (CGMS readings = 2.2 mmol/l) in calibration set left-A, values below 3.5 mmol/l were present in 99% (95% CI: 95-100%) of samples in left-B, 91% (95% CI: 84-96%) of samples in right-A, and 90% (95% CI: 83-95%) of samples in right B. In 84% of these episodes (95% CI: 59-96%) independent SMBG values were below 3.5 mmol/l. Difference in duration was observed with a median difference of 20 min; (left-A vs. right-B). CONCLUSION: Hypoglycaemic episodes recorded by CGMS are reproducible and agreement with independent SMBG values is acceptable for retrospective recording of hypoglycaemic events with CGMS.

Blood Glucose Self-Monitoring↗

Prediction of severe hypoglycaemia by angiotensin-converting enzyme activity and genotype in type 1 diabetes.

AIMS/HYPOTHESIS: We have previously shown a strong relationship between high angiotensin-converting enzyme (ACE) activity, presence of the deletion (D) allele of the ACEgene and recall of severe hypoglycaemic events in patients with Type 1 diabetes. This study was carried out to assess this relationship prospectively. METHODS: We followed 171 adult outpatients with Type 1 diabetes in a one-year observational study with the recording of severe hypoglycaemia. Participants were characterised by serum ACE activity and ACE genotype and not treated with ACE inhibitors or angiotensin II receptor antagonists. RESULTS: There was a positive relationship between serum ACE activity and rate of severe hypoglycaemia with a 2.7 times higher rate in the fourth quartile of ACE activity compared to the first quartile (p=0.0007). A similar relationship was observed for the subset of episodes with coma (2.9 times higher rate in fourth quartile compared to first quartile; p=0.048). The impact of serum ACE activity was most pronounced in C-peptide negative subjects (4.2 times higher rate in fourth quartile compared to first quartile; p=0.003), and in this subgroup carriers of the D allele of the ACEgene had higher rates of severe hypoglycaemia compared to the group homozygous for the insertion (I) allele. In a multiple regression analysis high serum ACE activity and impaired awareness of hypoglycaemia were identified as the only significant predictors of severe hypoglycemia. CONCLUSION: High ACE activity and the presence of the D allele of the ACE gene predict a high rate of severe hypoglycaemia in Type 1 diabetes.

Adult↗

Activity of angiotensin-converting enzyme and risk of severe hypoglycaemia in type 1 diabetes mellitus.

BACKGROUND: The insertion (I) allele of the angiotensin-converting-enzyme (ACE) gene occurs at increased frequency in endurance athletes. This association suggests that low ACE activity is favourable for performance in conditions with limited substrate availability. Such conditions occur in endurance athletes during competition and in diabetic patients during insulin-induced hypoglycaemia. Patients rely on preserved functional capacity to recognise hypoglycaemic episodes and avoid progression by self-treatment. We studied whether ACE activity is related to the risk of severe hypoglycaemia in type 1 diabetes. METHODS: Consecutive adult outpatients with type 1 diabetes, untreated with ACE inhibitors or angiotensin-II-receptor antagonists (n=207) reported their experience of mild and severe hypoglycaemia during the previous 1 year and 2 years. The patients were further characterised by diabetes history, degree of hypoglycaemia awareness, measurement of C-peptide, haemoglobin A(1c), and serum ACE concentrations, and determination of ACE genotype. FINDINGS: Patients with the DD genotype had a relative risk of severe hypoglycaemia in the preceding 2 years of 3.2 (95% CI 1.4-7.4) compared with those who had the II genotype. There was a significant relation between serum ACE activity and the rate of severe hypoglycaemia (relative risk per 10 U/L increment 1.4 [1.2-1.6]), corresponding to a 3.5 times higher risk for patients in the highest quartile than for those in the lowest quartile. Multiple regression analysis showed that the effect of the ACE genotype was explained by its influence on serum ACE activity and that the only other significant determinants of the risk of severe hypoglycaemia were the degree of hypoglycaemia awareness, b-cell function, and duration of diabetes of more than 20 years. INTERPRETATION: ACE activity is a clinically significant marker of the risk of severe hypoglycaemia in patients with type 1 diabetes, especially in those with impaired defence against hypoglycaemia. These findings need to be confirmed in prospective studies.

Adult↗

Primary gastrointestinal non-Hodgkin's lymphoma in adults: a population-based clinical and histopathologic study.

OBJECTIVES: To analyse the clinical course and the histopathology of primary gastrointestinal non-Hodgkin's lymphoma (GI-NHL) in adult patients and to investigate a possible impact of Helicobacter pylori. DESIGN/SETTING: Retrospective study of all adult patients in Copenhagen county diagnosed during a 6-year period with NHL. SUBJECTS: A total of 55 patients with GI-NHL diagnosed during the period from 1985 to the end of 1990. RESULTS: Twenty-eight patients had primary lymphoma in the stomach, 14 in the small intestine, 11 in the large intestine and two patients had multifocal involvement. The dominant presenting symptoms were abdominal pain, weight loss, diarrhoea, constipation and fatigue. Acute emergency problems such as severe haemorrhage or perforation at initial presentation were unusual. According to the revised European-American lymphoma (REAL) classification, diffuse large B-cell lymphoma was the most frequent histologic subtype comprising 53% of the cases. Helicobacter pylori infection was documented in 15 of 25 evaluable patients (60%) with gastric lymphomas and was not associated with any specific histological subtype. Endoscopic procedures and barium X-rays were the diagnostic approaches with highest sensitivity. In total, 30 patients (58%) achieved complete remission, 10 (19%) achieved partial remission, and 12 (23%) did not respond to treatment. The overall 5 year survival rate was 0.36 without statistically significant difference between the histological subtypes. Likewise the presence of Helicobacter pylori did not affect survival. CONCLUSION: Primary GI-NHL is a heterogeneous disease entity with considerable therapeutic controversies. No specific clinical or histological phenotype was associated with the presence of Helicobacter pylori.

Adult↗

Relationship between serum TSH and the responsiveness of toxic solitary autonomous thyroid nodules to radioiodine therapy.

OBJECTIVE: To investigate if serum TSH at the time of 131I therapy influences the outcome. DESIGN: A retrospective analysis of data on 39 consecutive patients with toxic solitary autonomous thyroid nodules treated with 131I during a 4 year period. METHODS: Serum TSH was determined by an ultrasensitive RIA with a functional sensitivity of 0.03 mU/l. The 131I dose was calculated blind to the actual serum TSH according to a model compensating for thyroid size estimated by palpation as well as 24 h 131I uptake. RESULTS: After a mean follow-up period of 30 months, 34 patients (87% of all patients) were euthyroid, three (8%) had responded insufficiently and required further antithyroid therapy, and two (5%) had developed hypothyroidism. No significant difference in the response pattern between patients with suppressed or detectable serum TSH could be demonstrated. The two patients who developed hypothyroidism both had detectable serum TSH at the time of 131I treatment. No other clinical parameter seemed to influence the outcome. CONCLUSION: There is no clinically significant effect of circulating TSH on the response of toxic solitary autonomous thyroid nodules to 131I therapy. However, keeping the patients subclinically hyperthyroid when receiving 131I treatment may possibly result in a reduced frequency of hypothyroidism.

Female↗

Drug-induced thrombocytopenia: clinical data on 309 cases and the effect of corticosteroid therapy.

OBJECTIVE: To analyse the clinical picture and the course of thrombocytopenia induced by non-cytotoxic drugs, and to evaluate a possible therapeutic effect of corticosteroids. METHODS: A retrospective analysis of 309 well-documented cases of drug-induced thrombocytopenia was performed. Data sources were reports from the files of the Danish Committee on Adverse Drug Reactions and discharge summaries. RESULTS: The median length of exposure to the offending drug, before development of thrombocytopenia, was 21 days. The median nadir platelet count was 11 x 10(9).l-1, and 74% of the patients had clinical haemorrhage. Bone marrow examination generally showed hyperplastic reactive changes and a variable number of megakaryocytes. Slight leucopenia was present in 6% of the patients and 16% were anaemic. Complete recovery was seen in 87% of cases, with a median recovery rate of 8 days. The standard treatment was corticosteroids, which were administered in 53% of the cases. No difference in recovery between corticosteroid-treated and untreated patients was observed. No other clinical parameter affected the recovery rate. The mortality rate due to haemorrhage was 3.6%. CONCLUSION: Thrombocytopenia induced by non-cytotoxic drugs is characterised by heterogeneous clinical picture and recovery is generally rapid. Although corticosteroids seem inefficient, we still recommend that severe symptomatic cases of drug-induced thrombocytopenia are treated as idiopathic thrombocytopenic purpura due to the difficult initial differentiation between the two conditions.

Adrenal Cortex Hormones↗

Serum TSH and the response to radioiodine treatment of toxic multinodular goitre.

A retrospective analysis of data from 73 consecutive patients with toxic multinodular goitre treated with iodine-131 (131I) during a 2-year period was performed to investigate if serum TSH at the time of 131I treatment influences the outcome. The dose of 131I was calculated according to a model compensating for thyroid size estimated by palpation and 24-h 131I uptake. Serum TSH was determined by a third-generation assay with a functional sensitivity of 0.03 mU/l. A significantly more pronounced response to 131I treatment was observed in patients with TSH > 0.0 mU/l than in patients with TSH = 0.0 mU/l (P = 0.0006. This difference resulted in a threefold lower frequency of non-responders and a fivefold higher rate of early hypothyroidism in the group with detectable serum TSH. While the high frequency of hypothyroidism among patients with measurable serum TSH can be explained by destruction of normal thyroid tissue, the high frequency of treatment failure in the group with serum TSH = 0.0 mU/l suggests that autonomous thyroid tissue may also be sensitized to a deleterious effect of 131I through stimulation by TSH. We conclude that serum TSH has a significant influence on the outcome of 131I treatment of toxic multinodular goitre. The results of 131I treatment may be improved by adjustment of the dose of 131I according to the serum TSH level, in addition to adjustment for goitre size and 24-h 131I uptake.

Female↗

[Pituitary function in hemochromatosis].

A review of the literature on pituitary function in haemochromatosis is presented. In morphological studies pituitary iron deposition, in particular in gonadotropic cells, has been demonstrated. In a number of case series, insufficiency of pituitary gonadotropic secretion with clinical hypogonadism was observed in 46% of the patients. Overt insufficiency of the other hormonal axes was infrequent. However, subclinical insufficiency of the growth hormone axis was present in 15%, of the lactotropic axis in 8%, of the thyroid axis in 4% and of the adrenocortical axis in 1.5% of the patients. Lactotropic, thyroid or adrenocortical insufficiency was usually associated with hypogonadism or growth hormone insufficiency. Investigation of pituitary function (in first line the gonadotropic and the somatotropic function) in patients with primary or secondary haemochromatosis is recommended on wide indications, in order to initiate relevant substitution therapy.

Hemochromatosis↗

Haemodynamic effects of eating: the role of meal composition.

1. The purpose of this study was to investigate the effect of fractional meal stimulation on postprandial haemodynamic changes, the possible correlation between these changes and the potential mediating role of circulating catecholamines and insulin. 2. Healthy young subjects were studied before and after ingestion of isocaloric, isovolumetric high-protein, carbohydrate or fat meals (80-85% of total energy), 60 kJ per kg of body weight. Multigated radionuclide cardiography with autologous 99mTc-labelled erythrocytes was performed for assessment of cardiac output, venous occlusion plethysmography to obtain forearm blood flow and Doppler-ultrasonography for portal vein flow. Plasma levels of catecholamines and insulin were determined by radioimmunoassay. 3. Cardiac output increased considerably after each meal, including the control meal (water) with only minor differences in extent and timing. Left ventricular volumes increased after food intake, most pronounced after carbohydrate and protein. Forearm blood flow increased only after carbohydrate and protein. Portal vein flow increased after all meals, especially after fat, but also after the control meal. There was a significant correlation between the increment in cardiac output and changes in forearm and portal vein flow, but no correlation between either haemodynamic response and plasma catecholamines or insulin. 4. Postprandial cardiovascular changes are not substantially different after various isocaloric and isovolumic meal compositions. Gastric distension seems to play a role in the increase in cardiac output, accomplished by ventricular dilatation. These changes seem to some extent to be linked to changes in muscle and splanchnic flow.

Adult↗

Thrombocytopenia induced by noncytotoxic drugs in Denmark 1968-91.

OBJECTIVES: To analyse the distribution of noncytotoxic drugs reported as cause of thrombocytopenia during a 24-year period, and to draw attention to the most commonly involved drugs in modern clinical practice. DESIGN/SETTING: Retrospective study of spontaneous case reports from the Danish reporting system on adverse drug reactions. SUBJECTS: A total of 309 critically reviewed cases of drug-induced thrombocytopenia reported during the period from 1968 to the end of 1991. RESULTS: Sodiumaurothiomalate and the combination sulfamethoxazole with trimethoprim were the most commonly reported single drugs, and nonsteroid anti-inflammatory drugs were the most frequently reported category of drugs. A pronounced shift in the spectrum of causal drugs was observed due to the introduction of new drugs and alterations in drug consumption. At present, valproic acid and measlesmumps-rubella vaccine are most numerously reported. The still-growing list of thrombocytopenia-inducing agents contained 110 different drugs. At present, 20% of reported cases concern drugs not previously registered as causing thrombocytopenia in Denmark. Twenty-five per cent of all cases were caused by drugs which appeared only sporadically in the material. CONCLUSIONS: The spectrum of drugs reported as causing drug-induced thrombocytopenia is broadening and changing progressively, reflecting changes in drug consumption. The most frequently reported drugs at present are valproic acid and measlesmumps-rubella vaccine.

Adolescent↗

Influence of meal composition on postprandial peripheral plasma concentrations of vasoactive peptides in man.

In a randomized cross-over study healthy non-obese male human subjects received standardized isocaloric, isovolumetric meals consisting of either carbohydrate, protein or fat and a non-caloric control meal consisting of an equal volume of water. Peripheral venous plasma concentrations of calcitonin gene-related peptide (CGRP), substance P (SP), vasoactive intestinal peptide (VIP), and peptide YY (PYY) were measured pre- and postprandially. Plasma CGRP concentrations were lowered following the protein meal and following the fat meal, but remained unaltered after carbohydrate or water ingestion. Plasma VIP concentrations increased slightly following the carbohydrate meal and following water loading. The PYY concentrations increased after the protein and the carbohydrate meal and a slight rise was observed following fat ingestion. Water loading did not affect the plasma level of PYY. We conclude that the postprandial peripheral plasma concentrations of CGRP, VIP and PYY are dependent on the caloric meal composition. The VIP, but not the CGRP and PYY concentrations seem to be influenced by gastric distension. The physiological significance of the postprandial alterations in peripheral concentrations of these peptides is at present uncertain.

Adult↗

Pain, tenderness, wheal and flare induced by substance-P, bradykinin and 5-hydroxytryptamine in humans.

The algesic effect of substance-P with and without the addition of bradykinin or 5-hydroxytryptamine was studied in 13 healthy volunteers. Test substances dissolved in saline were injected into the temporal muscle and the forearm skin and the effects compared with those of saline. In the temporal muscle, none of the test substances induced more pain than saline, but substance-P with bradykinin lowered the pressure pain threshold by 18% (p less than 0.02). All test substances induced pain wheal and flare in the forearm skin. Substance-P induced a more pronounced flare reaction than bradykinin, whereas the latter induced more pain than substance-P. This dissociation between pain and flare may indicate that C-fibres in the human skin represent more than one type of nociceptor.

Adult↗

Drug-specific characteristics of thrombocytopenia caused by non-cytotoxic drugs.

OBJECTIVE: To analyse drug-specific clinical characteristics and to investigate the possible influence of epidemiological and other factors on thrombocytopenia induced by selected non-cytotoxic drugs. METHODS: A retrospective analysis of drug-induced thrombocytopenia reported to the Danish Committee on Adverse Drug Reactions. One-hundred and ninety-two cases induced by the most frequently reported drugs were included and analysed from data extracted from report forms and discharge summaries. RESULTS: Pronounced drug-specific differences in the clinical appearance of thrombocytopenia were registered. Severe thrombocytopenia with haemorrhagic manifestations was reported following exposure to gold salts, non-steroid anti-inflammatory drugs, sulfonamide antibiotics, cinchona alkaloids and vaccines. Valproic acid-induced thrombocytopenia was dose-dependent. The differences were primarily determined by the drug itself and also by its usage pattern. No specific patient-related factor responsible for the heterogeneity of the clinical appearance of the adverse reaction was identified. Factors related to the physician, such as monitoring recommendations or level of attention towards the adverse reaction, seemed to be of little significance. CONCLUSION: The primary determinant of the clinical characteristics of thrombocytopenia induced by noncytotoxic drugs is the offending drug.

Adolescent↗