Gluco-regulatory response to intravenous glucose infusion in children undergoing surgery.
Explore the source record for details and available documents.
Adolescent↗
Biomedical subjects
M Knip
Publications and source records attributed to M Knip.
Extended HLA haplotypes in families with insulin-dependent diabetes mellitus in northern Finland.
Haplotypes including HLA, Bf and C4 loci were analyzed in a material comprising 55 families with diabetic children. One hundred and ten haplotypes found in IDDM patients were compared with 101 haplotypes present only in healthy family members. Two complotypes, BfSC4A3B3 and SC4A0B1, were significantly more common (P less than 0.05) in the diabetic haplotypes, and these were in most cases found in haplotypic combinations with HLA-B15,Dw4,DR4 and HLA-B8,Dw3,DR3 genes, respectively. The B8/DR3 haplotype was better conserved, as 72% included the BfSC4A0B1 complotype as compared with only 35% of the B15/DR4 haplotypes with "high risk" C4A3B3 complement alleles (p less than 0.05). DR3 was found in 26% of the diabetic haplotypes and DR4 in 43%. DR4 associated with the Dw4 in 69% of cases and with Dw14 in 26% of the diabetic haplotypes. Our results confirm that the two phenotypes found earlier to be associated with IDDM in Northern Finland, e.g. "B15,BfS,C4A3B3,Dw4,DR4" and "B8,Bfs,C4A0B1,Dw3,DR3" are inherited as haplotypes.
Diabetes Mellitus, Type 1↗
Postnatal decrease in insulin binding to erythrocytes in infants of diabetic mothers.
To clarify the role of insulin receptors in the macrosomia and the tendency to hypoglycemia in infants of mothers with insulin-treated diabetes mellitus (IDM) we studied insulin binding in erythrocytes from mixed umbilical blood and from peripheral venous blood collected when the infants were 3-14 days old. Normal infants were matched for gestational and postnatal age. The IDM infants were macrosomic, with significantly higher birth weights relative to gestational age than the control infants. Plasma free insulin concentrations in cord blood were 15-fold higher in the IDM than in the normal infants and more than 3-fold higher in the peripheral venous blood at the median age of 4 days. Hypoglycemia occurred in 12 of the 17 IDM and in none of the normal infants. In umbilical blood insulin binding to erythrocytes was similar in the IDM and normal infants. In both groups insulin binding decreased during the first postnatal weeks, but the decrease was significantly greater in the IDM than in the normal infants. The decrease in insulin binding to erythrocytes was a consequence of decreased receptor affinity as well as decreased receptor concentration in the IDM infants, but was mainly due to decreased receptor concentration in the normal infants. We conclude that insulin binding to its erythrocyte receptor in cord blood in IDM infants is similar to that in normal infants in spite of the simultaneous gross hyperinsulinemia in the IDM infants. The resulting increase in insulin action would then contribute to the tendency toward hypoglycemia and may be partly responsible for the macrosomia in IDM infants. The marked postnatal decrease in insulin binding in IDM infants is a possible explanation for their diminishing risk of hypoglycemia after the first few days of life in spite of persisting hyperinsulinemia.
Birth Weight↗
Variable plasma growth hormone (GH)-releasing hormone and GH responses to clonidine, L-dopa, and insulin in normal men.
The effects of synthetic GHRH-(1-44) (1 microgram/kg, iv), clonidine (0.15 mg/m2, orally), L-dopa (0.5 g, orally), and insulin (0.1 IU/kg, iv) on plasma immunoreactive (ir) GHRH and GH levels were determined in normal men, aged 31-46 yr (n = 4-8). In addition, plasma ir-GHRH and GH concentrations were determined before and after the administration of clonidine in six younger men, aged 19-25 yr. GHRH was extracted from plasma using Sep-Pak C18 cartridges and measured with a mid-portion-specific GHRH antiserum. The mean plasma ir-GHRH and GH levels ranged from 9-11 ng/L and 0.5-1.5 microgram/L, respectively, in the older men during a 2-h control study. After GHRH administration, the mean plasma ir-GHRH concentration increased to a peak of 512.5 ng/L at 3 min and GH to a peak of 9.2 micrograms/L at 10 min. Clonidine resulted in a significant increase in mean plasma GH levels (P less than 0.05) in the younger men, but not in the older men. Plasma ir-GHRH concentrations did not change after clonidine. L-Dopa increased plasma ir-GHRH at 60 min (P less than 0.05) and GH at 60-120 min (P less than 0.05). Insulin-induced hypoglycemia increased plasma GH levels (to a mean of 23.8 micrograms/L at 60 min; P less than 0.001), whereas plasma ir-GHRH levels did not change. We conclude that the mechanisms of the various GH stimulation tests differ. Some GH responses, including those induced by insulin, do not appear to be mediated by GHRH.
Adult↗
Serum aminoterminal propeptide of type III procollagen: a potential predictor of the response to growth hormone therapy.
The circulating concentrations of insulin-like growth factor I (IGF-I) and immunoreactive aminoterminal propeptide of type III procollagen (PIIINP) were measured in 12 children with short stature (8 GH deficient and 4 non-GH deficient) before and after 1 week, 5 weeks, and 3, 6, and 12 months of treatment with biosynthetic hGH. Seven children had a growth response (increase in relative growth velocity greater than 1.5 SD during the initial 6 months) to GH therapy (responders), whereas 5 failed to respond (nonresponders). No relationship was found between the pretreatment plasma IGF-I levels or their changes during therapy and the growth response. Serum PIIINP levels increased considerably in all but 3 children, after as little as 1 week of GH administration. After 5 weeks, all responders had an increase in their serum PIIINP concentrations of 40% or more, whereas the nonresponders had less or no increments. There was a close correlation between the GH-induced increase in serum PIIINP levels at 5 weeks and growth velocity after 6 months of GH therapy (r = 0.77; P less than 0.01). The correlation was even stronger with the growth velocity at 12 months (r = 0.83; P less than 0.001). The serum PIIINP response to short-term GH administration could be an early predictor of the growth response to long-term GH therapy. In contrast to plasma IGF-I, the PIIINP response may be useful both in GH deficient and non-GH deficient children.
Adolescent↗
Morphology, yield and functional integrity of islet-like cell clusters in tissue culture of human fetal pancreata obtained after different means of abortion.
Morphology, yield and function were studied in cultured islet-like cell clusters (ICC) from 140 human fetal pancreata obtained after abortions of different types performed at 11-23 weeks of gestation (12 by hysterotomy, 75 by mechanical dilation and extraction, and 53 induced with prostaglandin). After collagenase digestion and culture in medium supplemented with 10% human serum, up to 2000 free-floating ICC were formed from a single pancreas. Randomly scattered insulin- and glucagon-immunoreactive cells were found in the medullary part of the ICC. More than 100 ICC developed in 100% of the hysterotomies and 87% of the mechanical abortions, but in only 53% of the prostaglandin-induced abortions. Insulin and glucagon levels in the culture medium decreased rapidly during the first 7 days of culture, but then remained stable for at least 31 days. The hysterotomy-derived ICC responded to 10 mmol/l theophylline plus 20 mmol/l glucose by a 12.2 +/- 3.1 (SEM, N = 7) fold increase in insulin release, as compared with a 5.4 +/- 0.9 fold response of the prostaglandin ICC (N = 16; P less than 0.02). Despite the low proportion of B-cells, (pro)insulin biosynthesis accounted for 10% of the total protein biosynthesis in low (2 mmol/l) glucose. In conclusion, the yield and viability of the ICC were clearly better, if prostaglandin had not been used for the induction of the abortion.
Abortion, Induced↗
Effects of growth hormone and insulin-like growth factor I on endocrine function of human fetal islet-like cell clusters during long-term tissue culture.
The effects of recombinant human growth hormone (GH, 1 micrograms/ml) and insulin-like growth factor I (IGF-I, 200 ng/ml) on the production of insulin and glucagon by human fetal islet-like cell clusters (ICCs) were studied in tissue culture. ICCs were derived after collagenase digestion and culture of pancreases from 16 fetuses (mean gestational age 15.6 wk). The ICCs were cultured with or without GH or IGF-I for 7 or 31 days. Basal rates of insulin and glucagon production were not altered by GH during the first 17 days of culture, but the release of both hormones was increasingly augmented by GH during the last 2 wk of culture (131% increase in insulin and 85% in glucagon compared with controls). ICCs cultured for 7 days in the presence of GH secreted more insulin when incubated for 120 min in 20 mM than in 2 mM glucose (2.1-fold response, P less than .05), whereas ICCs maintained in basal medium did not respond to glucose. GH had no effect on DNA and insulin content or insulin biosynthesis. Exogenous IGF-I caused a 28% suppression of insulin release (P less than .05) between days 4 and 10 of culture but induced a 49% increase in the mean secretion rate during the last week (days 25-31, P less than .01). Glucagon release was not affected by exogenous IGF-I. In contrast to GH, exogenous IGF-I induced a twofold increase in the DNA content of the 7-day--cultured ICCs. However, insulin biosynthesis and release were markedly suppressed.(ABSTRACT TRUNCATED AT 250 WORDS)
Culture Techniques↗
Maturation of insulin response to glucose during human fetal and neonatal development. Studies with perifusion of pancreatic isletlike cell clusters.
The insulin release in response to glucose was studied in perifused isletlike cell clusters (ICCs) obtained from human fetal or neonatal pancreases at various stages of development: 12-15 gestational wk (n = 7), 17-20 wk (n = 13), 22.5 wk (n = 2, 1 diabetic pregnancy), and 26-44 wk (n = 6, postnatal samples). The ICCs were stimulated with 20 mM glucose and subsequently with 10 mM theophylline plus 20 mM glucose as a viability test. Insulin release increased to a detectable level (greater than 0.1 pg.ICC-1.min-1) during glucose stimulation in four of seven of the youngest fetuses. At 17-20 wk the basal rate of insulin release had increased by at least 15-fold above the detection limit (1.5 pg.ICC-1.min-1), and glucose promoted a sustained monophasic response that was on the average 1.6-fold higher than the basal level. The response was significant (P less than .05) in 9 of 13 experiments. With postnatal ICC (gestational age 26-44 wk), an early-phase peak response was observed in 5 of 6 experiments. The mean rates of insulin release after 5-12 min of glucose stimulation were 4.8 pg.ICC-1.min-1 in newborn infants and 2.1 pg.ICC-1.min-1 in 17- to 20-wk fetuses. The corresponding mean relative insulin responses (stimulated to basal) were 3.3-fold (range 1.1-7.5) and 1.6-fold (1.0-3.4), respectively (P less than .05, Mann-Whitney U test). The results suggest that the human fetal pancreas is already responsive to glucose during the first half of gestation, but the biphasic insulin release does not start to mature until the postnatal phase.
Cells, Cultured↗
[The diabetic fetus].
Explore the source record for details and available documents.
Diabetes Mellitus↗
Development of insulin antibodies, metabolic control and B-cell function in newly diagnosed insulin dependent diabetic children treated with monocomponent human insulin or monocomponent porcine insulin.
One hundred and thirty eight patients participated in a two-year randomized, double-blind multicentre trial to compare monocomponent human insulin and porcine insulin in the treatment of newly diagnosed insulin dependent diabetic children with respect to development of insulin antibodies, metabolic control and B-cell function. There was no difference between the two patient groups throughout treatment either in the level of IgG insulin binding or the percentage of patients with insulin antibodies (IgG-insulin greater than 0.012 U/l). However, the estimated mean of log insulin binding values in the antibody positive patients alone was significantly lower (p less than 0.05) in the human insulin treated group at all times apart from 1 and 18 months (e.g., human insulin group at one and two years: 0.104 and 0.152 U/l, porcine insulin group at one and two years: 0.162 and 0.212 U/l). The insulin antibodies in both patient groups bound equivalent amounts of human and porcine insulin tracer. Metabolic control, insulin dosage and B-cell function in the two treatment groups were similar throughout the treatment period. It is concluded that in newly diagnosed insulin dependent diabetic children monocomponent human insulin is slightly less immunogenic than monocomponent porcine insulin, and equally effective in overall metabolic control.
Animals↗
[Heterogenicity of type 1 diabetes in childhood].
Explore the source record for details and available documents.
Autoantibodies↗
Beneficial effects of palatable guar and guar plus fructose diets in diabetic children.
This randomized cross-over study evaluates the effects of extended, guar and guar + fructose diets on the metabolic balance of children with insulin-dependent diabetes mellitus (IDDM). We studied 22 children; mean age 12.2 years, mean duration of diabetes 4.4 years. The diet was supplement for three weeks with guar in palatable form (5% of daily carbohydrate intake) and with guar + fructose (1 g of fructose/kg body weight, max 30 g/d) for another three weeks. A control group (8 children, mean age 12.3, duration of diabetes 4.3 years) followed the same experimental protocol without guar supplementation. The metabolic balance was assessed by glucosuria index (per cent of tests with less than 1% glucosuria from all urine tests) and measurements of red cell glycohaemoglobin A1c (HbA1c). Serum total and HDL-cholesterol, C-peptide, pancreatic and enteroglucagon were also measured. HbA1c decreased during guar (p less than 0.001) and guar + fructose diet (p less than 0.001). The glucosuria index improved (p less than 0.02) and the serum total cholesterol concentration decreased (p less than 0.02) during the experimental guar diets. Guar in acceptable form and quantity in the diet appears to improve metabolic control of diabetic children.
Adolescent↗
Heat exposure elevates plasma immunoreactive growth hormone-releasing hormone levels in man.
The effects of heat exposure on plasma levels of GH and GHRH were studied in six younger (31-46 yr) and six older (49-66 yr) normal men. For the GHRH RIA, 2-mL plasma samples were purified on Sep-Pak C18 cartridges, from which the mean recovery of synthetic GHRH-(1-44) was 62 +/- 10% (+/- SD; n = 8). Heat exposure (15 min) in a Finnish sauna bath at an ambient temperature of 72 C, led to an increase in plasma GH levels from 2 to 5 micrograms/L (P less than 0.01) at 30 min in the younger men. Their rectal temperature had risen by 0.2 C at 15 min. Plasma immunoreactive GHRH increased from 9 to 36 ng/L (P less than 0.05) 5 min after heat exposure, and it gradually fell to the initial levels by 45 min. The older men did not have a significant increase in plasma GH or GHRH levels in response to the heat exposure. Reverse phase high pressure liquid chromatography studies of plasma immunoreactive GHRH suggested that the major circulating GHRH immunoreactivity was GHRH-(1-40). We conclude that heat exposure-stimulated GH release in young adult men is mediated by GHRH, but in older men, GHRH and GH responses do not occur.
Adult↗
Serum antibody-bound insulin as a measure of insulin antibodies in diabetic children.
The usefulness of the measurement of serum antibody-bound and total immunoreactive insulin (IRI) concentrations in the assessment of insulin antibodies was evaluated in a material comprising 49 insulin-dependent diabetic children with a mean age at onset of 8.6 years (range 0.8-16 years) treated with highly purified porcine insulins. Serum antibody-bound and total IRI concentrations of individual patients were compared with insulin antibody levels measured with 3 different insulin antibody assays. The correlation coefficients of insulin antibody levels with concentrations of serum antibody-bound IRI ranged from 0.75-0.79. In serum samples with moderate or high insulin antibody levels most of the insulin was in the form of insulin-insulin antibody immunocomplexes. Thereby a very close correlation was found between antibody-bound and total serum IRI concentrations (r = 0.98) in this material. Residual endogenous insulin secretion decreased with increasing duration of diabetes. No significant correlation was found between the duration of diabetes and serum antibody-bound IRI concentrations. High serum antibody-bound IRI concentrations were associated with low glucagon-stimulated plasma C-peptide levels. Although the determination of serum antibody-bound IRI concentrations does not characterize insulin antibodies with regard to binding capacity and affinity constants, it yields information of the actual degree of insulin binding in the circulation. This information may be useful in assessing the benefits of transferring diabetics with high insulin antibody titers from conventional to highly purified porcine or human insulin therapy.
Adolescent↗
Evidence of an accelerated B-cell destruction in HLA-Dw3/Dw4 heterozygous children with type 1 (insulin-dependent) diabetes.
The possible association between residual B-cell function and specific HLA antigens in Type 1 (insulin-dependent) diabetes was studied in a cross-sectional series of 144 diabetic children and adolescents, as well as in a prospective series of 44 newly diagnosed diabetic subjects who were observed for the initial 2 years of their diabetes. In the cross-sectional study, the HLA-Dw3/Dw4 heterozygotes had a lower mean serum C-peptide concentration during 1980, 0.03 +/- 0.01 nmol/l (mean +/- SEM) vs. 0.09 +/- 0.01 nmol/l (p less than 0.02), as well as a lower 24-h urinary C-peptide excretion, 0.27 +/- 0.06 nmol/m2 vs. 1.34 +/- 0.19 nmol/m2 (p less than 0.05), than the other subjects. In addition, the Dw3/Dw4 heterozygotes had a clinical remission of shorter duration, 113 +/- 47 days vs. 203 +/- 22 days (p less than 0.05), and a higher mean glycosylated haemoglobin level during 1980, 14.8 +/- 0.05% vs. 13.7 +/- 0.2% (p less than 0.05), than those without the Dw3/Dw4 combination. In the prospective study the serum C-peptide concentrations were of the same magnitude in the Dw3/Dw4 heterozygotes and the other subjects during the first month. Subsequently the C-peptide concentrations in the subjects with the Dw3/Dw4 combination started to decrease 2 months earlier than in the other subjects. The Dw3/Dw4 children had a significantly lower serum C-peptide concentration at 21 months, 0.01 +/- 0.01 nmol/l vs. 0.13 +/- 0.02 nmol/l (p less than 0.01), and at 24 months, 0.03 +/- 0.01 nmol/l vs. 0.12 +/- 0.02 nmol/l (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Increased platelet thromboxane B2 production in newborn infants of diabetic mothers.
Platelet thromboxane B2 (TxB2) production, plasma concentrations of C-peptide and pancreatic glucagon as well as blood glucose levels were measured in 12 infants of insulin-dependent diabetic mothers and eight healthy controls at the age of two hours. Platelet TxB2 production (p less than 0.05) and plasma C-peptide levels (p less than 0.02) were significantly higher and blood glucose concentrations lower (p less than 0.002) in the infants of the diabetic mothers than in the controls. The data suggest that platelets of infants of diabetic mothers produce increased amounts of proaggregatory thromboxane A2, which may contribute to the hyperaggregation in these infants.
Blood Glucose↗
HLA antigens and complotypes in insulin-dependent diabetes mellitus.
One hundred and thirty-six Finnish patients with insulin-dependent (type I) diabetes mellitus were investigated for the HLA-A, B, D and DR antigens as well as the Bf and C4 allotypes. The statistically significant increase in the frequencies of HLA-A9, B8, B15, Dw3, Dw4, DR3, DR4, C4A0 and C4B3 was observed when compared with the healthy controls. About 79% of the patients had HLA-DR4, and 53% had HLA-DR3 antigens. A rare C4 allele C4B3 was found in 21% of the patients, whereas only in 2% among the controls (relative risk 16.35). The etiological fraction (EF) values indicated that HLA D/DR alleles were the best markers for IDDM, the observed EF for HLA-DR4 in diabetes was as high as 0.70. Examination of HLA, Bf and C4 phenotypes suggested that at least two supratypes "B15 BfS C4A3B3 D(R)4" and "B8 BfS C4A0B1 D(R)3" were markers for the susceptibility to type I diabetes, one third of our patients had either of these supratypes. The protective role of DR2 and Dw2 antigens was also confirmed: no HLA-Dw2 positive patients and only one with HLA-DR2 was found.
Alleles↗
Erythrocyte insulin binding in preterm newborn infants.
To characterize the erythrocyte insulin receptor in newborn infants we studied the binding of 125I-insulin to the erythrocytes from 42 preterm infants (14 at birth, 14 aged 2-7 days, and 14 aged 8-16 days) with a mean gestational age of 34.1 wk, and from 32 term infants (16 at birth and 16 aged 2-7 days). The insulin binding to cord blood erythrocytes from preterm infants was significantly higher than that of cord blood cells from term infants and to postnatal cells from preterm as well as term infants. The erythrocytes from preterm infants aged 2-7 days bound more insulin than cells from preterm infants aged 8-16 days. The maximum insulin binding (specific insulin binding at tracer concentration of insulin) correlated negatively with the gestational age both at birth and over the 1st postnatal wk. In the preterm infants there was a strong negative correlation between the maximum insulin binding and postnatal age. The enhanced insulin binding to cord blood erythrocytes from preterm infants was due to both an increased receptor concentration and a high affinity for insulin. The increased affinity persisted over the 1st wk of life. In preterm infants older than 1 wk the insulin binding characteristics were basically similar to those in term newborn infants. In all infants studied the receptor concentration seemed to be postnatal age dependent while the receptor affinity was gestational age dependent. No correlation was found between the insulin binding data and the plasma concentrations of immunoreactive insulin or C-peptide.(ABSTRACT TRUNCATED AT 250 WORDS)
Blood Glucose↗