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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
PubMed1996

Proinsulin, C-peptide, and insulin in normal subjects during an 8-h hyperglycemic clamp.

Increased concentrations of proinsulin immunoreactive material (PIM) absolutely or relative to insulin is a characteristic finding in patients with non-insulin-dependent diabetes mellitus (NIDDM). The aim of this study was to test if 8 h or mild hyperglycemia (7-9 mmol/l) in healthy subjects could induce a preferential secretion of PIM from B cells. Serum concentrations of insulin, C-peptide and PIM were measured every 10 min during the 8 h of continuous glucose infusion in nine normal-weight healthy subjects without diabetes among their first-degree relatives. After a gradual rise in B-cell peptides, a steady state was reached. From 4 to 8 h no further difference in insulin, C-peptide or PIM concentration was found. Fasting PIM/C-peptide and PIM/insulin ratios of 0.5% and 2.3% increased during the glucose clamp to levels of 1.4% and 7.6%, respectively. Neither testing the regression slope nor comparing individual time points showed any significant difference for the PIM/C-peptide ratio from 2 to 8 h and for the PIM/insulin ratio from 3 to 8 h. These results do not support the hypothesis that an increased glucose drive per se results in an altered B-cell function with increasing PIM/C-peptide ratio. At least 8 h of mild hyperglycemia in healthy subjects does not progressively alter B-cell function.

Adolescent↗
PubMed1996

Increased molar proinsulin-to-insulin ratio in women with previous gestational diabetes does not predict later impairment of glucose tolerance.

OBJECTIVE: To evaluate if an increased proinsulin-to-insulin ratio (PI/I) in former gestational diabetes mellitus (GDM) subjects could be a marker for later impairment of glucose tolerance. RESEARCH DESIGN AND METHODS: This study is a prospective follow-up. In a previous follow-up study of former GDM subjects 3-4 years after an index pregnancy, an increased PI/I was found also in normoglycemic nonobese former GDM subjects compared with control subjects. A 75-g oral glucose tolerance test (OGTT) was performed 3 years after the first follow-up, i.e., 6-7 years after the index pregnancy in 97 of the former GDM subjects and in 23 control subjects. A 75-g OGTT according to the World Health Organization was performed. Glucose, insulin, proinsulin, and C-peptide were determined at 0, 30, 60, 90, 120, 150, and 180 min after the glucose intake. RESULTS: Since the first follow-up, an additional 3 in 97 (3.1%) and 15 in 97 (15.5%) of the former GDM subjects had NIDDM or impaired glucose tolerance (IGT), respectively. All control subjects still had a normal OGTT. The fasting PI/I at follow-ups 1 and 2 was significantly correlated in the former GDM subjects (r = 0.41, P < 0.001) and in the control group (r = 0.46, P < 0.05). There was no significant correlation between the PI/I in follow-up 1 and the fasting or 2-h glucose values at follow-up 2. If GDM subjects with a PI/I in the upper quartile in the first follow-up were compared with those with a lower PI/I, there were no significant differences in outcome of OGTT in the second follow-up. CONCLUSIONS: The hypothesis that an increased fasting PI/I is a marker for later development of NIDDM or IGT in former GDM subjects could not be supported.

Adult↗
PubMed1996

Proinsulin immunoreactivity in recent-onset IDDM: the significance of insulin antibodies and insulin autoantibodies.

OBJECTIVE: To study the natural history of fasting proinsulin immunoreactivity (PIM) during the first 30 months of IDDM and its relationship to fasting C-peptide and insulin antibodies. RESEARCH DESIGN AND METHODS: An incidence cohort of 204 consecutive newly diagnosed IDDM patients were followed prospectively, having blood drawn for measurements at diagnosis and at 1, 3, 6, 9, 12, 18, 24, and 30 months. A sensitive enzyme-linked immunosorbent assay was used for the determination of PIM. RESULTS: All patients had detectable fasting PIM in plasma at diagnosis, with a median value and interquartile range of 3.5 pmol/l (2.2-6.2). The median PIM level increased during the first months of IDDM to reach a peak at 9-12 months (9.9-10.3 pmol/l). PIM then declined gradually to 5.6 pmol/l (1.9-13.5) at 30 months without reaching baseline. PIM at each time point was widely scattered in a skewed log-normal distribution without signs of bimodality. After the onset of insulin treatment, median insulin antibody level increased and declined in a similar pattern. Both PIM and antibody level were significantly higher in children and adolescents compared with adults. However, stepwise multiple regression analysis showed that age was only of minor importance for the PIM variation during the study period. Insulin antibody level and fasting C-peptide were the major determinants at 3-30 months, accounting for approximately 40% of the variation (R2). Blood glucose was of minor importance, and insulin dose, HbA1c, and BMI were of no importance. The correlation between fasting PIM and fasting C-peptide improved (R2 doubled) if the insulin antibody level was accounted for. Further, the slope of the correlation curve between PIM and C-peptide increased threefold when antibody binding was > 4%. At diagnosis, insulin autoantibodies could be detected in 19% of the patients. Their presence predicted higher proinsulin at 1-3 months, a higher insulin dose the 1st year, and higher levels of insulin antibodies later in the study. CONCLUSIONS: Circulating insulin antibodies may affect the level of PIM in IDDM, probably by adding a pool of IgG-bound PIM thereby increasing half-life and plasma concentration. This may explain why C-peptide and PIM levels do not change in concert during the 1st years of IDDM. Unlike C-peptide, PIM can not therefore quantitate beta-cell secretion unless the presence of insulin antibodies is ruled out.

Adolescent↗
PubMed1995

Bcl-2 protein expression in breast cancer in relation to established prognostic factors and other clinicopathological variables.

BACKGROUND: Bel-2 inhibits most kinds of programmed cell death and provides a selective survival advantage to various cell types. Bcl-2 is physiologically expressed in ductal epithelia of the normal breast. The biological significance of Bcl-2 (over)expression for the development and progression of breast cancer has still to be evaluated. PATIENTS AND METHODS: A series of 133 primary breast cancers was investigated for expression of the Bcl-2 protein by immunohistochemistry of paraffin-embedded tissue sections. Results were correlated with other variables of established or presumed predictive value. RESULTS: A significant positive correlation was observed between Bcl-2 expression and positivity for estrogen and progesterone receptors (p < 0.001). High proliferative activity as assessed by Ki-67 staining correlated inversely with Bcl-2 expression (p < 0.001). Bcl-2 immunostaining was not related to positivity for c-erbB-1. It was negatively associated with overexpression of c-erbB-2 (p = 0.04), whereas a strong positive correlation was found with expression of c-erbB-3 (p = 0.01). There was a significant inverse correlation between histological grading and immunoreactivity for Bcl-2 (p < 0.001). N0 tumors tended to be Bcl-2 positive, but differences were not statistically significant. CONCLUSION: Bcl-2 was detected predominantly in differentiated tumors. Expression was associated with other favorable histopathological features and predictors of positive clinical outcome. Loss of Bcl-2 expression seems to be linked to loss of hormonal regulatability, increased dedifferentiation and deregulated proliferation.

Breast Neoplasms↗
PubMed1995

Proinsulin immunoreactivity in identical twins discordant for noninsulin-dependent diabetes mellitus.

Disproportionate elevation [increased proinsulin/insulin (PI/INS) ratio] of PI immunoreactivity is associated with noninsulin-dependent diabetes mellitus (NIDDM). The nature of this abnormality is not known. To address the question of whether genetic factors contribute to hyperproinsulinemia, we measured fasting levels of PI immunoreactivity, intact INS, and C peptide (CP) in 12 pairs of monozygotic twins discordant for NIDDM for a mean (+/- SEM) period of 9 +/- 3 yr. Thirteen age- and body mass index-matched healthy subjects without any family history of NIDDM acted as controls. The nondiabetic twins had levels of fasting INS, CP, PI, PI/CP, and PI/INS similar to those of control subjects. Fasting levels of PI, and PI/CP and PI/INS ratios were significantly 2- to 3-fold elevated in NIDDM twins compared to those in both nondiabetic twins and control subjects. To investigate whether hyperproinsulinemia in these NIDDM patients was due to a differential elevation of intact PI or conversion intermediates, we analyzed PI profiles in NIDDM twins and normal subjects by high pressure liquid chromatography. PI was heterogeneous and consisted mainly of des(31,32)-PI and intact PI in both NIDDM patients and normal subjects, with no major difference in composition between the groups. Small amounts of des(64,65)-PI (0-11%) were measured in some patients and normal subjects. The results suggest that hyperproinsulinemia is not a genetically determined trait per se in NIDDM. Disproportionately elevated PI levels seem to be related to the actual disease process. Further conversion of intact PI and des(31,32)-PI may be equally impaired in NIDDM.

Adult↗
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↗