Biomedical subjects

M Knip

Publications and source records attributed to M Knip.

At least 253 records · Page 14Linked to original sources

PubMed1986

Serum insulin-releasing activity and the Prader-Willi syndrome.

Pathogenesis and etiology of the various clinical features of the Prader-Willi syndrome (PWS) are not completely understood. There is evidence suggesting a hypothalamic abnormality leading to hypogonadism in this syndrome. To test the possible hypothalamic involvement in the pathogenesis of obesity in these patients we studied the sera of 5 patients with PWS for insulin-releasing activity of possible hypothalamic origin. In addition 4 patients with a PWS-like syndrome and 6 obese patients with signs of central nervous system damage were studied. All five patients with PWS showed significant insulin-releasing activity in their sera. Of the four patients with PWS-like symptoms three showed similar activity while three of the obese patients with central nervous system damage had this activity in their sera. Serum insulin-releasing activity has been shown earlier to be associated with childhood obesity and it could play a role in the pathogenesis of obesity in PWS.

Adolescent↗

PubMed1986

Relation between insulin antibody and complement-fixing islet cell antibody at clinical diagnosis of IDDM.

To test the hypothesis that insulin-binding antibodies (IBAs) appearing in the circulation before insulin treatment are markers of beta-cell damage, we studied the prevalence of IBAs and both conventional (IF-ICAs)-and complement (CF-ICAs)-fixing cytoplasmic islet cell antibodies in 60 newly diagnosed diabetic children with a mean age of 9.5 yr. Seventeen (28.3%) had an insulin binding exceeding the upper range (2.8%) of that observed in 68 age-matched controls. The IBA-positive subjects were characterized by a younger age of onset [6.2 +/- 4.0 (SD) vs. 10.8 +/- 3.2 yr; P less than 0.001], lower glycosylated hemoglobin A1 levels (14.1 +/- 3.1 vs. 16.0 +/- 3.0%; P less than 0.05), lower serum C-peptide concentrations (0.12 +/- 0.07 vs. 0.20 +/- 0.17 nmol/L; P less than 0.05), and an increased frequency of HLA-Dw4 (9/13 vs. 11/37; P less than 0.05). There was no significant relation between IBAs and serum C-peptide concentrations after age adjustment by multiple regression analysis. Forty-three children (75%) were positive for IF-ICA and 38 (63.3%) for CF-ICA. Twelve IBA-positive diabetics (70.6%) had IF-ICA as well as CF-ICA in their serum. No association could be observed between IBA and either IF-ICA or CF-ICA, however. The results suggest that IBAs developing before diagnosis serve as an indicator of clinical and genetic heterogeneity within IDDM rather than as a marker of autoimmune beta-cell destruction.

Adolescent↗

PubMed1986

Sulphonylureas and glucose metabolism in phenobarbital induced rats.

The addition of phenobarbital (PB) to a sulphonylurea (SU) regimen may improve glycemic control in patients with non- insulin dependent diabetes mellitus (NIDDM, type II). Since SU reactions may be modified, we investigated glucose metabolism in rats with combined PB and SU treatment. Chlorpropamide (CHL) and glibenclamide (GB) were selected as SU drugs. The combination of PB to the CHL or GB regimens induced the drug metabolism enzymes excluding aminopyrine N-demethylase activity, which was enhanced by GB but not CHL. The CHL and GB treatments lowered blood glucose (BG) concentration and decreased hepatic glucose-6-phosphate phosphohydrolase (G6P hydrolase) activity and glycogen reserves in the rats. The concomitant administration of PB and the SUs decreased hepatic G6P hydrolase activity and glycogen content in the animals, whereas the BG level remained unaltered. The hepatic glycogen content was decreased more markedly in the CHL plus PB than in the CHL alone treated animals. The findings suggests that enzyme inducers modify the action of SU in rats. Hepatic drug and glucose metabolizing enzymes seems also to respond to distinct PB plus SU combinations in different ways.

Aminopyrine N-Demethylase↗

PubMed1986

Physical activity and fitness in obese children.

Daily physical activity and physical fitness were studied in 31 obese and 31 normal-weight children matched for age and sex. The ages of the children ranged from 5.7 to 16.1 years. The history of their physical activity was examined using a questionnaire completed by the child and the parents. Physical fitness was measured using a two-stage exercise test on a bicycle ergometer. There were no significant differences in daily activities between the obese and the non-obese children, while the sports grades at school were lower and participation in the training teams of sports clubs was less frequent among obese than normal-weight subjects. The obese children were physically less fit than the normal-weight subjects as judged from the pedalling time in exercise test (P less than 0.05) and from the maximum oxygen consumption (VO2 max) related to lean body mass (LBM) (P less than 0.001). Twenty-seven children participated for 1 year in a weight-reduction programme which comprised individual nutrition counselling, guidance on physical activities and supportive therapy. The reduction in weight was successful in 25 out of 27 children and VO2 max increased on average from 44.2 to 47.1 ml/min/kg of LBM (P less than 0.025). There was no change in the time used for physical activities during the weight reduction period although the children's participation in the training teams of sports clubs increased. It was concluded that obese children are less fit than their non-obese counterparts. Weight reduction results, however, in an improvement of the maximum oxygen consumption towards normal.

Adolescent↗

PubMed1985

Plasma six-keto-prostaglandin F1 alpha and endocrine pancreatic function in the newborn infant of the diabetic mother.

Plasma concentrations of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), C-peptide and pancreatic glucagon and blood glucose levels were measured in 13 infants of insulin-dependent diabetic mothers at the age of 2 h. Plasma 6-keto-PGF1 alpha levels were lower in these infants when compared to those of healthy controls at the same age (p less than 0.05). Plasma 6-keto-PGF1 alpha correlated negatively with the C-peptide levels (r = -0.57; p less than 0.05) and positively with the pancreatic glucagon concentrations (r = 0.83; p less than 0.001) in the infants of diabetic mothers. No correlation with blood glucose concentrations was found. The data suggest that hyperinsulinemia in infants of diabetic mothers is associated with a decreased vascular prostacyclin production.

6-Ketoprostaglandin F1 alpha↗

PubMed1984

Evidence of delayed beta-cell destruction in type 1 (insulin-dependent) diabetic patients with persisting complement-fixing cytoplasmic islet cell antibodies.

Forty-four children with Type 1 (insulin-dependent) diabetes (aged 0.7-16.7 years) were observed from diagnosis for cytoplasmic islet cell antibodies and serum C-peptide concentrations. Islet cell antibodies were analysed by indirect immunofluorescence for both conventional IgG and complement-fixing antibodies. Thirty-seven children (84%) were found to be positive for conventional islet cell antibodies at diagnosis, and 21 (48%) remained positive over the observation period. Twenty-six patients (59%) were positive for complement-fixing antibodies at diagnosis and eight remained so during the follow-up period. The serum C-peptide concentrations increased significantly during the first 3 months after diagnosis, after which there was a gradual decrease in the levels. Those children who remained positive for complement-fixing antibodies over the observation period had significantly higher serum C-peptide concentrations on several occasions during the second year and had also a higher integrated serum C-peptide concentration over the initial 2 years than those who became negative for complement-fixing antibodies. These observations suggest that the continuous production of complement-fixing islet cell antibodies in those patients who are positive for these antibodies at diagnosis presupposes the preservation of a sufficient amount of functioning beta cells for antigenic stimulation. These results support the view that the complement-fixing islet cell antibodies reflect ongoing destructive processes in the beta cells.

Adolescent↗

PubMed1984

Immunogenicity of monocomponent human and porcine insulin in newly diagnosed type 1 (insulin-dependent) diabetic children.

The aim of the present study was to compare the immunogenicity of monocomponent human insulin with that of monocomponent porcine insulin in newly diagnosed Type 1 (insulin-dependent) diabetic children. One hundred and thirty-five patients at diagnosis of diabetes (age 1-18 years, mean age 9.3 years) were randomly allocated to treatment with either Monotard MC + Actrapid MC or Monotard HM + Actrapid HM in a double-blind trial conducted in Sweden, Finland, Norway and Denmark. The human and porcine insulin groups were identical at diagnosis with respect to age, sex and measures of metabolic control. At all times the mean insulin antibody levels and the percentage of antibody-positive patients were lower in the human group compared with the porcine group. At 3 and 12 months, the insulin antibody values were significantly lower in the human group than in the porcine group (p less than 0.05, Wilcoxon's rank sum test). At 12 months, antibody values in the human group ranged from 0 to 1.2 U/l (mean 0.14 U/l) and in the porcine insulin group from 0-5.2 U/l (mean 0.63 U/l). It is therefore concluded that human monocomponent insulin has a lower immunogenicity than porcine insulin of the same purity in newly diagnosed diabetic children during the first year of insulin treatment.

Adolescent↗

PubMed1984

Analysis of pancreatic peptide hormones by reversed-phase high-performance liquid chromatography.

Reversed-phase high-performance liquid chromatography (HPLC) is examined as a method for separating pancreatic peptides. The method was based on gradient elution with acetonitrile in an acid phosphate buffer (pH 3.10). Apart from human and porcine insulin all the other peptide standards tested (thyrotropin-releasing factor, vaso-active intestinal polypeptide, human C-peptide, porcine C-peptide, somatostatin, porcine glucagon, porcine proinsulin and porcine pancreatic polypeptide) could be separated simultaneously in 40 minutes with a binary gradient composed of five linear segments and increasing from 0 to 60% acetonitrile. Human and porcine insulin could be almost completely resolved by a minimal reduction in the steepness of the acetonitrile gradient. Repeated injections of human C-peptide and porcine insulin resulted in a coefficient of variation of less than 1.5% in the retention times. The use of 125I-labelled peptides gave recoveries exceeding 90%. HPLC of acid ethanol extracts of autopsy pancreases from three infants showed that the immunoreactivity of the peptides measured remained unaffected by the chromatography. Both immunoreactive C-peptide and immunoreactive insulin (IRI) were recovered in two peaks, the second common peak representing proinsulin and amounting to 6.5 to 8.4% of total IRI. Immunoreactive glucagon was eluted in a single peak. Chromatography of plasma extracts from two infants of diabetic mothers demonstrated that proinsulin accounted for 59-63% of total IRI, while insulin was separated into two peaks corresponding to the standards of human insulin and porcine insulin. These results indicate that reversed -phase HPLC is a method with a good reproducibility and a high recovery applicable to the rapid and effective separation of pancreatic peptides from biological extracts.

Animals↗

PubMed1984

Metabolic control in children and adolescents with insulin-dependent diabetes mellitus.

The metabolic control, assessed from the mean daily glucosuria, mean daily glucosuria index based on home tests, and mean haemoglobin A1 (HbA1) concentrations during 1980, and the influence of various factors on the control were analysed in 177 diabetic children and adolescents. The mean daily glucosuria was 21% of the carbohydrates in the subscribed diet, and the mean glucosuria index 55%. The mean HbA1 was 14.0%. Boys had better metabolic control than girls. Good motivation towards treatment was associated with better metabolic control. There was a negative correlation between metabolic control and both the age of the child and the duration of diabetes. Prepubertal children were better controlled than those in puberty. Adherence to the dietary regimen was related to better control, as was the patient's endogenous insulin secretion, measured by serum C-peptide concentration. There was also an association between the season and the metabolic control, the control being better in the spring than during the other seasons. On the basis of these results male sex, a good motivation towards treatment, residual beta-cell function and adherence to the prescribed diet favor good metabolic control, while a long duration of the disease, the presence of puberty and relatively high age in childhood are factors impairing the metabolic control.

Adolescent↗

PubMed1984

Physical fitness of children and adolescents with insulin-dependent diabetes mellitus.

The physical working capacity (PWC170) of 84 children and adolescents with insulin-dependent diabetes mellitus (IDDM) and of 94 non-diabetic subjects was measured by a submaximal progressive exercise test. The age of the diabetic subjects ranged from 6.3 to 18.8 years and that of the control subjects from 8.5 to 18.8 years. The PWC170 of diabetic boys was lower than that of non-diabetic boys (p less than 0.01) while no difference was observed between diabetic and non-diabetic girls. PWC170 was inversely related to age (p less than 0.01) and concentration of hemoglobin A1 (p less than 0.025) in diabetic boys but not in diabetic girls. No relationship was observed between PWC170 and duration of diabetes in either boys or in girls. The results indicate that good physical fitness in boys is associated with a better metabolic control. Hence the study indirectly supports previous observations that physical activity improves the metabolic control of IDDM.

Adolescent↗

PubMed1983

Partial purification of an insulin-releasing activity in human serum.

An activity that enhances insulin release from perifused rat pancreatic islets has recently been isolated from human serum fractions (molecular weight 1,000-5,000 daltons). To characterize this activity we have studied the insulin-releasing effect of serum subfractions from obese and non-obese children obtained by reversed-phase high-performance liquid chromatography (HPLC). The serum insulin-releasing activity eluted in the HPLC system at 12-13 minutes, which corresponded to the retention time of the tridecapeptide insulin-glucagon liberin isolated from bovine hypothalamus. Insulin-releasing activity was found in serum subfractions from both obese and normal-weight children. The relative insulin-releasing potency of the active subfractions was higher than that of the original total serum fractions, indicating the presence of some substance(s) which inhibit insulin secretion in the total serum fractions. Oral glucose loading increased the relative insulin-releasing activity in the HPLC subfractions from obese children. This study suggests that the insulin secretagogue in human serum might be identical to hypothalamic insulin-glucagon liberin as these substances behave similarly on reversed-phase HPLC and have parallel insulin-releasing properties.

Animals↗

PubMed1983

Relation of enteroinsular hormones at birth to macrosomia and neonatal hypoglycemia in infants of diabetic mothers.

To study the role of enteroinsular hormones in fetal macrosomia and neonatal hypoglycemia in infants of diabetic mothers, we measured plasma concentrations of free and total immunoreactive insulin, C-peptide, pancreatic glucagon, enteroglucagon, and gastric inhibitory polypeptide at birth in 35 IDMs and 35 infants of normal mothers. Twenty fasting adults of normal weight were also studied. Sixteen IDMs were macrosomic at birth; 17 developed neonatal hypoglycemia over the first postnatal hours. The IDMs had ten times higher concentrations of free IRI than the normal infants in cord blood. Free IRI concentrations were related to the severity of maternal diabetes, with the infants of white class D to F mothers having the highest levels. The IDMs with macrosomia had a twofold increase in the concentrations of free IRI when compared with IDMs of normal weight. There was a significant correlation between the birth weight ratio and the concentrations of free IRI. The IDMs who developed neonatal hypoglycemia had considerably higher concentrations of free IRI than did normoglycemic IDMs. The decrease of blood glucose over the first postnatal hours correlated strongly with the free IRI concentrations in the cord blood. The IDMs had a threefold increase of the C-peptide concentrations over those in normal infants. Six IDMs had a molar ratio of C-peptide to free IRI of less than 1. Both the IDMs and normal infants had substantially higher concentrations of enteroglucagon and lower concentrations of GIP than did the fasting adults. Our data provide direct evidence that IDMs are markedly hyperinsulinemic at birth and that ambient hyperinsulinemia plays a crucial role in the development of fetal macrosomia and neonatal hypoglycemia. Moreover, the observed discrepancy in the relative increase of free IRI and C-peptide, combined with the low molar ratio of C-peptide to IRI, suggests a decreased metabolic clearance of insulin or transplacental passage of insulin from the maternal circulation in infants of mothers with insulin-treated diabetes.

Adult↗

PubMed1983

Pancreatic islet cell function and metabolic control in an infant with permanent neonatal diabetes.

A girl with typical clinical manifestations of neonatal diabetes was observed for 16 months with consecutive evaluations of pancreatic beta- and alpha-cell function and metabolic control. At the diagnosis both the plasma immunoreactive insulin (IRI) and C-peptide concentrations were inappropriate for the contemporaneous hyperglycemia. During the follow-up, the C-peptide fell twice below the detection limit but the beta-cell function recovered partially on both occasions. Based on 24-hour urinary C-peptide excretion, the endogenous insulin secretion was less than 10% of that in non-diabetic infants. When diagnosed the patient had plasma immunoreactive glucagon (IRG) and glucagon-like immunoreactivity (GLI) concentrations below the reference range for normal neonates. The IRG normalised within the first month, while the GLI increased to a level exceeding the reference range. Hemoglobin A1 had already risen at the time of diagnosis and subsequently rose to a level indicating poor metabolic control. The findings indicate an immature function of both beta- and alpha-cells at the diagnosis with the alpha-cells maturing within the first month. The recovery of the beta-cell function, after two failures in this patient with permanent neonatal diabetes, suggests that the beta-cell damage was at least partially reversible.

Diabetes Mellitus, Type 1↗

PubMed1983

Erythrocyte insulin binding in normal infants, children and adults.

To establish normal insulin binding criteria, we studied the binding of insulin to erythrocytes from normal subjects of different ages. Insulin binding to cord erythrocytes and to erythrocytes from infants aged 2-7 days was significantly higher at tracer and physiological insulin concentrations than was binding to cells from children aged 1-15 years and adults. In infants aged 1-12 months the maximum insulin binding to erythrocytes was significantly higher than that to erythrocytes from children, and in addition, it correlated negatively with age. An increase in receptor concentration was found in cord erythrocytes whereas an increased receptor affinity for insulin was found in erythrocytes from infants. Insulin binding characteristics in erythrocytes from prepubertal and pubertal children were basically similar to those in women. Erythrocytes from men bound significantly higher amounts of insulin than did those from women. This difference was associated with changes in receptor affinity for insulin. There was no correlation between the insulin binding characteristics and the circulating concentration of insulin or C-peptide. The increased erythrocyte insulin binding at birth persisted over the neonatal period. There was an overall negative correlation between the maximum insulin binding and age in the subjects studied, but the major decrease in erythrocytes insulin binding occurred during the first year of life past the neonatal period. These observations stress the importance of using age-matched controls in studies on erythrocyte insulin binding in disease states.

Adolescent↗

PubMed1983

Basal insulin secretion and erythrocyte insulin binding in preterm and term newborn infants.

To study the ontogeny of the insulin secretion and the erythrocyte insulin receptor we measured plasma immunoreactive insulin and C-peptide concentrations and the binding of [125I]-insulin to the erythrocytes in cord blood from 16 preterm and 16 term infants. 20 normal-weight adults were also studied. The C-peptide concentrations and the molar ratio of C-peptide to insulin were lower in the newborn infants than in the adults. The immunoreactive insulin correlated positively with birth weight in the term infants. The insulin binding to erythrocytes from the newborn infants was increased when compared to the adults. Erythrocytes from the preterm infants bound more insulin than the cells from the term infants. There was a strong negative correlation between insulin binding and gestational age. In the term infants, plasma C-peptide correlated negatively with the insulin binding. The increased binding to erythrocytes from the term infants was due to an increase in the receptor concentration. The high insulin binding in the preterm infants was a result of both an increased receptor concentration and affinity. These data suggest that the basal insulin secretion is similar in preterm and term infants and that the clearance of insulin is decreased in newborn infants. The increased insulin binding in newborn infants may be a mechanism by which the growth stimulatory effect of insulin in fetal life is mediated.

Adult↗

PubMed1983

An association between complement-fixing cytoplasmic islet cell antibodies and endogenous insulin secretion in children with insulin-dependent diabetes mellitus.

Cytoplasmic islet cell antibodies and endogenous insulin secretion were studied in 184 children and adolescents having insulin-dependent diabetes mellitus (IDDM) in a cross-sectional study. The mean age of the subjects was 12.3 yr (range: 2.8-19.2 yr), and the mean duration of diabetes was 4.6 yr (range: 0.1-15.6 yr). Islet cell antibodies (ICA) were determined by both the indirect immunofluorescence (IF-ICA) and the complement-fixing (CF-ICA) methods. Forty-four patients (23.9%) were positive with respect to both IF- and CF-ICA, 54 patients (29.3%) had only IF-ICA, and 86 patients had no ICA. The patients having CF-ICA had a significantly higher endogenous insulin secretion in comparison with the patients who were only IF-ICA positive. The difference between the groups remained significant even when the age at onset of diabetes and the duration of the disease were taken into account. This finding, revealing an association between CF-ICA and endogenous insulin secretion, suggests that complement-fixing antibodies are seen only if the beta-cell mass is sufficiently preserved. The result contradicts the hypothesis, based on studies in vitro, that CF-ICA should be involved in the selective beta-cell damage in IDDM.

Adolescent↗

PubMed1982

Postinitial remission in diabetic children--an analysis of 178 cases.

We studied 178 diabetic children and adolescents diagnosed during the period 1962-79 to find out the occurrence and duration of the postinitial remission, factors favoring a remission and the prognostic value of the remission. A postinitial remission occurred in 113 children (64%) being complete in only three boys (2%). The duration ranged from one month to 4.8 years, the mean being 8.4 months. The boys had a remission more often and of longer duration than the girls. The duration of diabetes was longer in the children without remission. The children with remission had lower blood glucose, milder hyperketonemia and ketonuria, higher pH and PCO2 at onset than those without remission. Hemoglobin A1 (HbA1) during 1979 were lower in the children with a positive remission history. The children with a remission lasting more than one year had a subsequently higher glucosuria index, lower HbA1 and higher C-peptide when compared to those without remission or to those with a short remission. The remission frequency increased from 1962 to 1979. Male sex and mild metabolic derangement at onset favor a postinitial remission, which results in a persisting residual beta-cell function and better metabolic control beyond the remission.

Adolescent↗

PubMed1982

Hormonal and metabolic effects of intravenous infusion of prostacyclin in healthy women.

To study the hormonal and metabolic effects of prostacyclin (PGI2), 6 healthy women were infused iv with PGI2 (1, 2, 4, and 8 ng/kg/min. each for 20 min) dissolved in glycine buffer, or with glycine buffer only. Serial blood samples collected before, during and after the infusion were assayed for FSH, LH, prolactin, growth hormone, thyrotrophin, oestradiol, progesterone, testosterone, cortisol, thyroxine, triiodothyronine, renin, aldosterone, glucose, insulin, glucagon, cholesterol, high density lipoprotein-cholesterol, triglycerides, alkaline phosphatase, alanine and aspartate aminotransferases, bilirubin, sodium, potassium, chloride, calcium, inorganic phosphorous, creatinine and uric acid. PGI2 infusions were accompanied by increased levels of prolactin, growth hormone and cortisol, probably due to the stressful side-effects during PGI2 infusion. In addition, plasma renin activity, glucagon and blood glucose increased, whereas the other variables measured did not change. These PGI2-effects should be kept in mind, when PGI2 is used in clinical practice.

Adolescent↗