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Biomedical subjects

C Binder

Publications and source records attributed to C Binder.

At least 55 records · Page 3Linked to original sources
PubMed1994

Disproportionately elevated proinsulin levels precede the onset of insulin-dependent diabetes mellitus in siblings with low first phase insulin responses. The Childhood Diabetes in Finland Study Group.

The objective of this study was to test whether levels of proinsulin immunoreactivity (PIM) relative to those of insulin immunoreactivity (IRI) or C-peptide are changed and related to subclinical beta-cell dysfunction in siblings of insulin-dependent diabetes mellitus (IDDM) patients. Twenty-three siblings, previously found positive for islet cell antibodies and/or insulin autoantibodies, were divided into 2 groups according to their first phase insulin response (FPIR) to i.v. glucose tolerance tests (IVGTTs) sequentially performed during an observation period of 2 yr. Eleven siblings had diminished FPIR on at least 1 occasion (group 1), whereas 12 siblings had a normal FPIR on all occasions studied (group 2). All underwent a further IVGTT (0.5 g glucose/kg BW), and serum samples were taken at 0, 1, 3, 6, 10, 20, 30, 40, 50, and 60 min. The 2 groups had comparable median age, female/male ratio, weight, height, fasting blood glucose, immunoreactive insulin, C-peptide, and insulin autoantibodies levels, but group 1 had significantly higher islet cell antibodies levels. Fasting median PIM/IRI and PIM/C-peptide ratios were 2- to 3-fold higher in group 1 [10.5% (range, 1.8-93.8%) vs. 5.2% (range, 1.9-14.3%) and 3.3% (range, 0.4-23.1%) vs. 1.3% (range, 0.7-2.6%; P < 0.05]. Fasting PIM/C-peptide ratios correlated inversely with FPIRs (rs = -0.68; P < 0.01). During glucose stimulation, maximal responses of IRI and C-peptide were 4-fold lower in group 1, and the time of maximal responses of IRI and C-peptide occurred later in group 1 than in group 2. In contrast, no difference in maximal responses of PIM was found, but the time of maximal responses of PIM occurred later in group 1. Nine of 11 siblings in group 1 presented with IDDM 1-28 months after the test, compared to none in group 2. In group 1 a paradoxical inhibitory response of PIM was observed during the first 6 min of the IVGTT. These data indicate that fasting PIM/IRI and/or PIM/C-peptide ratio reflects subclinical beta-cell dysfunction in prediabetic subjects with evidence of immunological beta-cell assault and suggests that an elevated ratio may be an additional marker for later development of IDDM.

Adolescent↗
PubMed1993

[Necrotizing hepatitis with a fatal outcome after carbimazole therapy].

A 74-year-old woman developed weakness, lack of appetite and abdominal swelling 7 months after starting treatment with carbimazole (10 mg/d for 10 weeks) and, subsequently, radioiodine for hyperthyroidism. Physical examination revealed generalized oedema and ascites. Computed tomography showed a liver of normal size but infiltrated by nodules up to 4 cm in diameter. Erythrocyte sedimentation rate was raised and there were abnormal concentrations of haemoglobin, total proteins, liver enzymes and creatinine, as well as decreased platelet and white cell counts. Thyroid function was normal. Viral and autoimmune diseases were largely excluded. Liver biopsy showed a severe, highly active hepatitis with parenchymal necroses, large-drop fatty infiltration and intralobular granuloma-like inflammatory reactions, as well as lympho-histiocytic inflammation of the portal areas. The most likely cause was the carbimazole treatment. In addition to symptomatic treatment she received prednisone (1 mg/kg), because an allergic diathesis could not be excluded. But she died of hepatic failure 6 weeks after admission.

Aged↗
PubMed1993

Proportional proinsulin responses in first-degree relatives of patients with type 2 diabetes mellitus.

Elevated fasting proinsulin immunoreactive material (PIM) has previously been found in patients with type 2 (non-insulin-dependent) diabetes mellitus. It is not known whether this is a genetic trait or whether it is related to the manifestation of type 2 diabetes. Neither is it clear whether the raised fasting insulin immunoreactivity previously observed in first-degree relatives of patients with type 2 diabetes is due to raised PIM. Furthermore, it has not been investigated whether first-degree relatives have altered PIM responses to different secretagogues. To study this, PIM, insulin and C-peptide were measured in patients with type 2 diabetes, in their first-degree relatives and in healthy control subjects in the fasting state and in relatives and controls during a hyperglycemic clamp. At the end of the hyperglycemic clamp, 0.5 mg of glucagon was given intravenously to stress the beta cells further. Fasting PIM concentrations were significantly higher in patients with type 2 diabetes (P < 0.05). These patients did not have significantly elevated fasting insulin levels when corrected for PIM. In the relatives, fasting insulin concentrations were elevated but PIM levels were normal suggesting that the increase in fasting insulin concentrations reflected an increase in true insulin. The incremental PIM, insulin and C-peptide responses to glucose and glucagon in the relatives were not different from those in the controls. We conclude that elevated fasting PIM levels in patients with type 2 diabetes seem not to be a genetic trait.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Proinsulin levels in newborn siblings of type 1 (insulin-dependent) diabetic children and their mothers.

Elevated proinsulin levels have been observed in healthy first degree relatives of Type 1 (insulin-dependent) diabetic patients. This elevation could reflect a sequele after a previous attack on the beta-cells not necessarily leading to diabetes, or represent a family trait related to the development of diabetes. When cord plasma levels of proinsulin, insulin and C-peptide from 14 newborn siblings of Type 1 diabetic patients were compared with 21 newborn control siblings unrelated to diabetic subjects, no differences were observed. Neither were any differences observed between their mothers at delivery when comparing the same parameters. In cord plasma the proinsulin levels (median and range) were higher than those in plasma from 35 adult fasting women unrelated to diabetic subjects (10, 5-83 pmol/l vs 4, 2-33 pmol/l; p < 0.001) whereas the C-peptide levels (median and range) were lower (0.20, 0.11-0.56 nmol/l vs 0.37, 0.21-0.69 nmol/l; p < 0.001). No differences in insulin levels using a highly specific insulin assay were observed. The results suggest that newborn children have high proinsulin and low C-peptide levels unrelated to heredity of diabetes and that the previously described elevated proinsulin level observed in older first degree relatives of diabetic subjects occurs later in life.

Adult↗
PubMed1993

Identification of mycobacterial isolates by thin-layer and capillary gas-liquid chromatography under diagnostic routine conditions.

The mycolic acid patterns of 75 strains of mycobacteria belonging to 46 different species were studied by thin-layer chromatography (TLC). Additionally, the mycolic acid pyrolytic cleavage products were determined by capillary gas-liquid chromatography (C-GLC). Eleven different patterns based on number, type and Rf values of the detected lipid spots were identified. The mycolic acid methyl ester profiles of clinical isolates were compared with those of reference strains. In this way, it was possible to relate these clinical isolates to mycobacterial groups defined by their mycolic acid profiles. The 11 patterns and the methods used are described in detail.

Chromatography, Gas↗
PubMed1993

Decreased beta-cell function in women with previous small for gestational age infants.

Insulin, proinsulin and C-peptide responses to intravenous glucose (glucose infusion test, GIT) and insulin sensitivity were measured in women who previously and for unexplained reasons gave birth to small-for-gestational-age infants (SGA, n = 10) or appropriate-for-gestational-age infants (AGA, n = 11). Insulin sensitivity was evaluated by two different methods, somatostatin-, insulin- and glucose infusion test (SIGIT) and Bergman's minimal model method applied to the frequently samples intravenous glucose tolerance test. The two groups were comparable with regard to age, parity and body mass index. The SGA group exhibited significantly (p < 0.01) lower early (0-10 min) and late (10-60 min) insulin, C-peptide and proinsulin responses during GIT than were seen in the control AGA group. Insulin sensitivity evaluated by the two techniques was increased in the SGA group, significantly so only with the minimal model method. The insulin sensitivity index (Si) according to Bergman was 10.98 +/- 2.10 in the SGA as compared to 4.36 +/- 1.18 x 10(-4)min-1 x uU-1 in the AGA group (antilogged values +/- 95% confidence intervals). Early insulin response (GIT) and Si values were inversely correlated (r = -0.48, p < 0.05).

Adult↗
PubMed1993

Nocturnal versus diurnal hormonal counterregulation to hypoglycemia in type 1 (insulin-dependent) diabetic patients.

UNLABELLED: Asymptomatic hypoglycemia in IDDM patients seems to be more frequent during the night than during the day, with reported frequencies as high as 56%. Hormonal counterregulation to diurnal and nocturnal hypoglycemia was studied in 10 insulin-dependent diabetic patients without diabetic complications in order to test whether hormonal responses were lower at night than during daytime. A lower catecholamine response might imply less marked symptoms and therefore one reason why patients are not awakened by hypoglycemia. Blood glucose was stabilized to around 6 mmol/l by iv insulin infusion and hypoglycemia was induced by increasing the insulin infusion rate--in the night studies at 01.30, in the day studies at 08.00. Blood glucose nadirs were 1.5 +/- 0.4 (1.2-1.9) mmol/l at night and 1.9 +/- 0.3 (1.3-2.2) mmol/l during the day; in the three patients the nadirs were identical during both the night and day. One patient had no adrenaline response to daytime hypoglycemia. In general, nocturnal hypoglycemia elicited greater catecholamine responses correlated to the duration of hypoglycemia. Glucagon responses showed a great heterogeneity independently of diabetes duration and hypoglycemic level. Growth hormone secretion was reduced during the night study; however, no refractory periods were found after sleep-related growth hormone secretion. IN CONCLUSION: counter-regulatory hormonal responses tend to be greater at night than during the day and do not explain why patients are not awakened by nocturnal hypoglycemia.

Adult↗
PubMed1993

Highly sensitive enzyme immunoassay of proinsulin immunoreactivity with use of two monoclonal antibodies.

A highly sensitive two-site sandwich ELISA measuring total proinsulin immunoreactive material in serum or plasma was developed. The assay was based on two monoclonal antibodies, an anti-C-peptide antibody bound to a microtest plate and a biotin-labeled anti-insulin antibody. The detection limit (3 SD above zero value) in buffer was 0.05 pmol/L, corresponding to 0.25 pmol/L in human serum (diluted 1:5). The linear calibrator range was 0.05-20 pmol/L. Interassay CVs were 4.7% at a median (range) of 2.3 pmol/L (1.4-2.8 pmol/L, n = 8), 6.7% at 5.1 pmol/L (3.3-8.0 pmol/L, n = 8), and 8.7% at 10.0 pmol/L (8-12 pmol/L, n = 10). Mean analytical recovery of added human proinsulin (hPI) (2, 5, and 10 pmol/L) to serum was 84% (range 68-128%, n = 9). Human insulin and human C-peptide did not cross-react at 5000 and 10,000 pmol/L, respectively. The four major proinsulin conversion intermediates reacted 65-99%: split(32-33)hPI 74%, des-(31,32)hPI 65%, split(65-66)hPI 78%, and des(64,65)hPI 99%. All serum values from 38 fasting healthy subjects were above the detection limit: median (range) 4.0 (2.1-12.6) pmol/L.

Adult↗
PubMed1992

Cognitive function in type 1 (insulin-dependent) diabetic patients after nocturnal hypoglycaemia.

UNLABELLED: Eight Type 1 (insulin-dependent) diabetic patients with no diabetic complications were studied on two consecutive and one subsequent overnight occasions. The aim was to evaluate the influence of nocturnal hypoglycaemia on neuropsychological and reaction time tests the following morning. Hypoglycaemia was induced by i.v. insulin infusion, blood glucose nadir was 1.5 +/- 0.3 mmol/l. Duration of hypoglycaemia (blood glucose less than 3 mmol/l) was 101 +/- 38 min. Whole night sleep statistics for all patients showed no statistical differences between the normoglycaemic and hypoglycaemic nights, however, there was a tendency of prolongation of the second sleep cycle in the nights with hypoglycaemia. Each patient was used as his own control and periods with blood glucose concentration less than 3 mmol/l were compared to exactly the same periods in nights with blood glucose level over 5 mmol/l. During hypoglycaemia the amount of deep sleep was reduced and replaced by superficial sleep and arousals of short duration. Further, the reduction in deep sleep was replaced later at night. Neuropsychological test scores and reaction time measurements in the morning showed no differences between the normoglycaemic and hypoglycaemic nights. IN CONCLUSION: despite sleep disturbances, nocturnal hypoglycaemia did not impair cognitive function the following morning in Type 1 (insulin-dependent) diabetic patients.

Adult↗
PubMed1992

Combined deficiencies of the pyruvate dehydrogenase complex and enzymes of the respiratory chain in mitochondrial myopathies.

In six patients with mitochondrial (encephalo-) myopathy investigations of skeletal muscle revealed a defect of pyruvate dehydrogenase complex (PDHC) in combination with one or more respiratory chain complex deficiencies. A combination of defects of this kind has not been reported previously. Five of the six patients presented within the 1st year of life and had a severe clinical course. Intrafamilial variability of the clinical course in dizygotic twins both suffering from a cytochrome c oxidase deficiency and one of them also from a PDHC deficiency suggests an additional effect of PDHC deficiency on the clinical symptoms. Immunoblot studies of PDHC in five of the patients revealed no abnormalities in their subunit pattern, rendering a defect of mitochondrial protein import or assembly unlikely. The finding of a combined PDHC and respiratory chain deficiency has implications for the diagnostic approach, for therapy and genetic counselling. The exact pathogenetic mechanism of this combination of defects remains to be elucidated.

Female↗
PubMed1992

Nasal glucagon in the treatment of hypoglycaemia in type 1 (insulin-dependent) diabetic patients.

The aim of this study was to compare the effect of nasally administered glucagon in doses of 1 (A) and 2 mg (B), with 1 mg glucagon administered intramuscularly (C) in 12 C-peptide-negative IDDM patients. Spontaneous recovery (D) from insulin-induced hypoglycaemia in the same patients was used as reference. The mean age was 31.1 (21-48) years, diabetes duration 10.8 (2.7-31) years and HbA1c 7.7 (6.5-9.8)%. Hypoglycaemia was induced by i.v. insulin infusion. When blood glucose (BG) reached about 2 mmol/l either glucagon was administered or the patients recovered spontaneously. BG nadir was 1.6 (1.1-2.3) mmol/l. BG increments during the first 15 min after glucagon administration were: (A) 1.9 +/- 0.7 (0.4-3.0); (B) 2.5 +/- 0.7 (1.5-3.5); (C) 2.5 +/- 1.0 (1.2-4.7); and (D) 0.3 +/- 0.4 (0-1.0) mmol/l, respectively. All treatments were more effective, measured as increments in BG, than spontaneous recovery, P less than 0.00001. There was no difference between nasal treatment with 2 mg (B) and i.m. treatment (C), both being more effective than 1 mg (A) nasal treatment, P less than 0.1. BG continued to increase up to 10 mmol/l 90 min after i.m. glucagon administration, whereas it stabilized at a level of 4.6-6 mmol/l, 30-45 min after nasal administration. Eighty percent of the patients had side-effects to nasal administration - local irritation, rhinitis or sneezing. Half of the patients sneezed, without correlation with the delivered dose of glucagon. None of the patients had side-effects which would preclude further treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intranasal↗
PubMed1992

Endocrine emergencies. Hypoglycaemia.

Hypoglycaemia is possibly the most frequent metabolic emergency, in that insulin-induced hypoglycaemia is a common side-effect of treatment of a common disease. The symptoms are partly sympathetic and related to the release of catecholamines. These symptoms include sweating, tremor, palpitations, sensation of hunger, restlessness and anxiety. Other symptoms are caused by an insufficient supply of glucose to the brain, resulting in neuroglucopenia with symptoms like blurred vision, weakness, slurred speech, vertigo and difficulties in concentration. Symptom recognition is the primary and most effective defence against cerebral dysfunction which is the ultimate consequence of hypoglycaemia. Even in insulin-treated diabetic patients symptom failure might occur. Patients who experience severe episodes of hypoglycaemia do not constitute a special subgroup of patients. However, near-normalization of blood glucose levels have resulted in an increase in the incidence of severe hypoglycaemia. Moreover, the threshold for hormonal counter-regulatory responses in adrenaline, growth hormone and cortisol is lowered after a period of strict metabolic control in insulin-dependent diabetic patients. The glucose level at which the patients become subjectively aware of hypoglycaemia is correspondingly reduced. Other reasons for hypoglycaemia to occur are oral hypoglycaemic agents, especially sulfonylureas which may be potentiated by other drugs. Prolonged hypoglycaemia may be seen after first-order sulfonylureas, and may indicate glucose infusion as treatment. Next to insulin and sulfonylurea, ethanol is the most common cause of hypoglycaemia. In non-diabetics, hypoglycaemia will typically develop 6-24 h after a moderate or heavy intake of ethanol by a person who has had an insufficient intake of food for 1 or 2 days. Insulin-producing tumours, insulinomas and non-islet cell tumours may also be reasons for hypoglycaemia in non-diabetics. Treatment of mild episodes of hypoglycaemia is intake of fast-absorbing carbohydrates. Severe episodes can be treated with either i.v. dextrose or glucagon injected i.m. or i.v. The glycaemic response and recovery of a normal level of consciousness is 1-2 min slower after glucagon than after glucose.

Emergencies↗
PubMed1992

Homogeneity in pattern of decline of beta-cell function in IDDM. Prospective study of 204 consecutive cases followed for 7.4 yr.

OBJECTIVE: To study the natural history of beta-cell function from onset of IDDM to expected deterioration of insulin (C-peptide) secretion and to identify different patterns of decline, if any. RESEARCH DESIGN AND METHODS: A cohort of 204 consecutive newly diagnosed IDDM (clinical criteria) patients were followed prospectively for 7.4 yr (range 6-9 yr), measuring fasting C-peptide at onset, 1, 3, 6, 9, 12, and then every 6 mo until 106 wk (range 104-135 wk). Then, postprandial C-peptide was measured. RESULTS: Fasting C-peptide was 0.17 nM (range 0.11-0.25 nM) at onset followed by an annual increase rate of 0.16 nM/yr (range 0.06-0.48 nM/yr) to a peak of 0.28 nM (range 0.23-0.34 nM/yr) after 25 wk (range 12-39 wk). The subsequent annual decline rate of fasting C-peptide was 0.08 (0.05-0.12) and of postprandial C-peptide 0.03 nM/yr (range 0.02-0.06 nM/yr). None of these parameters showed bimodality in their distribution. However, some parameters were important. In men, fasting C-peptide at onset was lower, but the initial C-peptide increase rate was more pronounced compared to women. Furthermore, insulin-free remission was related to higher C-peptide levels throughout the study. C-peptide was higher during the 1st yr of diabetes in subjects greater than 30 yr of age at onset compared with younger diabetic patients. Stepwise multiple regression analysis showed that age, male sex, and fasting C-peptide at onset were of some predictive value for the C-peptide levels at 5 yr. However, simple group comparisons revealed no significant differences. CONCLUSIONS: No major heterogeneity exists in the pattern of decline of beta-cell function in IDDM, although small differences in pattern could be identified in both sexes, in different age-groups, and in relation to achieving insulin-free remission.

Adult↗
PubMed1991

Separation and quantitation of serum proinsulin and proinsulin intermediates in humans.

Two reversed-phase high-performance liquid chromatographic (RP-HPLC) systems were developed for the separation of human insulin, proinsulin and the major proinsulin intermediates. The individual components were quantified using two enzyme-linked immunosorbent assays for insulin and proinsulin immunore-active material (PIM) after (passive) evaporation of the organic modifier. Serum samples from normal subjects and patients with non-insulin-dependent diabetes mellitus were immunopurified and analysed in one of the RP-HPLC systems. The proportion of PIM relative to insulin immunoreactive material was higher in the diabetic patient compared with that in the normal subject. In both, PIM was heterogeneous, consisting of intact proinsulin and des-proinsulin intermediates.

Chromatography, High Pressure Liquid↗
PubMed1991

Respiratory tract infections due to different rhinovirus serotypes and the influence of maternal antibodies on the clinical expression of the disease in infants.

Rhinoviruses were isolated from nasopharyngeal secretions of 49 children hospitalized because of severe respiratory tract infection. The isolates were typed using 90 type-specific antisera. No obvious relation between certain serotypes and the severity of illness was found. Serum samples were drawn from all children simultaneously with the nasopharyngeal secretions and screened for the presence of type-specific neutralizing antibodies. Children aged 1 week to 6 months had higher neutralizing antibody titers and revealed a lower degree of morbidity than older children. The decline of neutralizing serum antibodies with increasing age was correlated with a higher incidence of severe disease in those aged 7-12 months. Nevertheless, also in this age group children with mild clinical courses of disease were observed despite a low concentration or an absence of neutralizing serum antibodies. This indicates that not only neutralizing serum antibodies, but other factors also influence the clinical expression of RHV-induced disease.

Antibodies, Viral↗
PubMed1991

Nocturnal electroencephalogram registrations in type 1 (insulin-dependent) diabetic patients with hypoglycaemia.

Eight Type 1 (insulin-dependent) diabetic patients with no diabetic complications were studied overnight for two consecutive and one subsequent night with continuous monitoring of electroencephalogram and serial hormone measurements. The aims were: 1) to evaluate the influence of spontaneous and insulin-induced hypoglycaemia on nocturnal electroencephalogram sleep-patterns and, 2) to evaluate counter-regulatory hormone responses. Spontaneous hypoglycaemia occurred on six nights (38%) with blood glucose concentrations less than 3.0 mmol/l and on four nights less than 2.0 mmol/l. All the patients experienced insulin-induced hypoglycaemia with a blood glucose nadir of 1.6 (range 1.4-1.9) mmol/l. The electroencephalogram was analysed by a new method developed for this purpose in contrast to the traditional definition of delta-, theta-, alpha- and beta-activity. The blood glucose concentration could be correlated to the rank of individual electroencephalogram-patterns during the whole night, and specific hypoglycaemic amplitude-frequency patterns could be assigned. Three of the eight patients showed electroencephalogram changes at blood glucose levels below 2.0 (1.6-2.0) mmol/l. The electroencephalogram classes representing hypoglycaemic activity had peak frequencies at 4 and 6 Hz, respectively, clearly different from the patients' delta- and theta-activity. The changes were not identical in each patient, however, they were reproducible in each patient. The changes were found equally in all regions of the brain. The three patients with electroencephalogram changes during nocturnal hypoglycaemia could only be separated from the other five patients by their impaired glucagon responses. Against this background the possibility of protection by glucagon, against neurophysiologic changes in the brain during hypoglycaemia may be considered.

Adult↗