[Influence of non-diabetic pregnancy on fructosamine and HbA1c concentration]. / Der Einfluss der nichtdiabetischen Schwangerschaft auf die Fructosamin- und HbAIc-Konzentration.

HbAIc and fructosamine concentrations were measured in the course of 177 nondiabetic pregnancies and compared with the corresponding values of 24 nondiabetic nonpregnant women. In all three trimesters HbAIc and fructosamine were significantly lower than the corresponding values in the nonpregnant women; HbAIc: 1st trimester 4.77 +/- 0.62%, 2nd trimester 4.38 +/- 0.59%, 3rd trimester 4.33 +/- 0.49%, p < 0.01; fructosamine 1st trimester 2.13 +/- 0.17 mmol/l, 2nd trimester 2.02 +/- 0.15 mmol/l, 3rd trimester 1.90 +/- 0.15 mmol/l, p < 0.01; nonpregnant women: HbAIc 5.13 +/- 0.41%, fructosamine 2.53 +/- 0.17 mmol/l. However, if the fructosamine is correlated to the respective total protein concentration a constant value results for the course of pregnancy. The changes in the HbAIc and fructosamine concentrations in pregnancy should be taken into account when treating pregnant diabetics.

Influence of diabetic neuropathy on skin microcirculation assessed by transcutaneous oxymetry.

Skin microcirculation was investigated in 45 patients with long term diabetes and with severe, moderate or no neuropathy, and in 15 controls. Transcutaneous oxygen pressure (tcPO2) measurements on the forefoot were performed at 37 degrees C to assess local capillary flow at rest, during leg dependency and reactive hyperaemia, and also at 44 degrees C, including the response to oxygen inhalation. TcPO2 (37 degrees C) at rest was significantly elevated with an increasing degree of neuropathy (Controls: 4.8 +/- 3.7; patients without neuropathy: 4.2 +/- 2.9; with moderate neuropathy: 6.0 +/- 2.9 (p < 0.01); with severe neuropathy: 7.2 +/- 4.2 mmHg (p < 0.001)). Leg dependency resulted in a decrease of tcPO2 in the controls, while an increase was observed in 18.6% of the measurements in patients, reflecting a disturbed vasoconstrictor response. Regardless of neuropathy, absolute tcPO2 values during reactive hyperaemia were reduced in all patient groups as well as tcPO2 (44 degrees C) and its increase during oxygen breathing. Diabetic neuropathy is likely to increase local capillary flow, while the other differences to healthy controls may be contributed to a microcirculation disorder independent of neuropathy.

[Fructosamine as a parameter for monitoring carbohydrate metabolism in the treatment of diabetes mellitus]. / Fructosamin als Parameter des Kohlenhydratstoffwechsel-Monitoring in der Therapie des Diabetes mellitus.

Fructosamine, protein, albumin and HbA1c from 199 diabetics were followed for up to 220 days. An increase in average blood glucose during the preceding 10 days causes an increase in fructosamine by 50 mumol/l. During the day there is little variation in the fructosamine concentration, whereas relating fructosamine to protein or albumin results in substantial fluctuations. A possible cause is the necessity for two measurements which is associated with an increased error. Long term observations reveal a significant correlation between fructosamine and HbA1c which is little affected by relating fructosamine to protein or albumin. Diabetics exhibited significantly lower protein and albumin concentrations than the normal collective, yet the standard deviations from the individual means were only 7 and 7.9%, respectively.

Assessment of insulin action in man: role of hyperglycemia.

The effect of hyperglycemia on insulin-induced glucose metabolism (M) was investigated in healthy subjects using sequential clamp protocols at constant insulin + somatostatin infusions and varying plasma glucose. During euglycemia (4.8 mmol/l) M increased from 5.6 to 12.5 mg.kg-1.min-1 with increasing plasma insulin (0.34-3.00 nmol/l). At increasing glucose (6.7 mmol/l), M further increased (9.7 to 19.2 mg.kg-1.min-1) with the plasma insulin level (0.41 to 2.99 nmol/l). At a plasma glucose level of 9.8 mmol/l insulin (0.42 to 3.17 nmol/l) was still effective to increase M (13.7 to 25.2 mg.kg-1.min-1). Regression analysis showed that hyperglycemia does not only increase the maximal insulin-stimulated M, but also decreases the insulin concentration causing a half maximum effect. During prolonged clamp studies M increased by about 10% per h, independent by the plasma glucose level. We conclude that hyperglycemia increases M by increasing insulin responsiveness as well as insulin sensitivity. Data derived from euglycemic clamp studies alone are of limited value with respect to the assessment of insulin action.

Glucoregulatory function of thyroid hormones: interaction with insulin depends on the prevailing glucose concentration.

The effect of elevated serum thyroid hormone concentrations on insulin-induced glucose metabolism was studied in healthy subjects before and after T4 administration (250 micrograms T4/day for 10-14 days). This treatment induced moderate hyperthyroidism (T4, 15.2 micrograms/dl; T3, 200 ng/dl). The following results were obtained. Insulin receptor binding to a 90% enriched monocyte fraction or to mitogen-stimulated cultured T lymphocytes was decreased by T4 administration, whereas insulin binding to erythrocytes was unaffected. Despite down-regulation of cellular insulin receptors, T4 administration did not alter oral glucose tolerance, but increased the disappearance of glucose after an iv load and the amount of glucose metabolized during euglycemic clamp studies infusing 1.0 or 1.5 mU insulin/kg BW X min; no effect was found at insulin infusion rates of 0.5, 2.0, and 4.0 mU/kg X min. At increasing steady state plasma glucose levels (up to 175 mg/dl) and an insulin infusion rate of 1.0 mU/kg BW X min, T4 administration reduced insulin-induced glucose metabolism. We conclude that experimental hyperthyroidism decreases insulin receptor binding but increases insulin-induced glucose metabolism during euglycemia. This may be due to the direct effect of thyroid hormones on glucose metabolism; however, during hyperglycemia, thyroid hormone induced insulin resistance is unequivocal.

Ion-exchange chromatography of amino acids in ejaculates of diabetics.

30 amino acids and their derivatives could be found in the ejaculates of humans by ion-exchange chromatography. There were significant differences between diabetics and controls in the levels of threonine, serine, glutamine, glycine, iso-leucine, leucine, tyrosine, phenylalanine, histidine and in 3-methyl-histidine. There was a positive correlation between levels of certain amino acids and the number of pathologically motile spermatozoa, particularly microforms and head alterations. An impaired Krebs cycle function may explain an elevation of amino acid levels as they are utilized mainly by this cycle, which function depends on intact substrate flow from glucose catabolism.

[Effect of pregnancy on maternal carbohydrate and lipid metabolism. II: Changes in lipid and carbohydrate metabolism as well as hormonal changes following intravenous glucose administration]. / Untersuchungen zum Einfluss der Schwangerschaft auf den Kohlenhydrat- und Fettstoffwechsel der Mutter. Teil II: Anderungen im Lipid- und Kohlenhydratmetabolismus sowie hormonale Veränderungen nach intravenöser Glucosegabe.

The following parameters of glucose biokinetics in pregnancy, in which the behavior of the glucose in the steady state is described, were investigated mathematically following short-term disturbance of the steady state of the maternal metabolism by intravenous administration of glucose. The glucose assimilation coefficient (KG) is unchanged in pregnancy. However, both during pregnancy and post partum (2.30; 2.20; 2.36; 1.79 [%/min]), the values are higher than in the non-pregnant control group (1.2%/min). Analogously to these findings, the glucose distribution space increases during pregnancy from 13 liters to 16.3 liters, decreasing post partum to 13.4 liters. The easily exchangeable glucose pool, i.e., the quantity available for assimilation in the distribution space, is unchanged during pregnancy; nor is there any change as compared to the non-pregnant and postpartal control groups. Glucose transfer, i.e., the glucose quantity which enters or leaves the pool per unit of time, is increased during pregnancy (0.45; 0.444; 0.47 [g/kg/h]) as compared to the non-pregnant and postpartal controls (0.25; 0.35 [g/kg/h]). The findings above indicate that the maternal glucose metabolism is increased during pregnancy. Owing to the lipolytic effect of HPL, the mother is obliged to meet a portion of her energy requirements from the lipid metabolism, so that there is enough glucose available for the fetus. HPL appears to develop this glucose-saving effect doubly.(ABSTRACT TRUNCATED AT 250 WORDS)

[Effect of pregnancy on carbohydrate and lipid metabolism of the mother--I. Kinetics of various parameters of carbohydrate and lipid metabolism and of various hormones as a function of the length of pregnancy]. / Untersuchungen zum Einfluss der Schwangerschaft auf den Kohlenhydrat- und Fettstoffwechsel der Mutter--Teil I: Die Kinetik einzelner Parameter des Kohlenhydrat- und Fettstoffwechsels sowie verschiedener Hormone in Abhängigkeit vom Schwangerschaftsalter.

Numerous factors influence fetal weight increase and growth. To permit a discussion of biochemical influences on fetal growth, maternal substrates and hormones which influence lipid and carbohydrate metabolism were measured and their relationships were analyzed. In 173 patients the following substrates were measured between the 8th and 40th week of pregnancy: glucose in whole blood and urine, glycerin, triglycerides, total cholesterol, free cholesterol and the hormones HGH, HPRL, HPL, IRI and estriol (E3). A group of nonpregnant and a group of recently delivered women served as controls. The glucose concentration in the whole blood of the mother diminished during pregnancy from 88.3 mg/100 ml to 77.4 mg/100 ml (2 alpha less than 0.05, r = 0.47, n = 77). It was still below the value for the non-pregnant controls post partum (63.6 mg/100 ml as compared to 92.3 mg/100 ml). Glucosuria increased during pregnancy, reaching a maximum in the second trimester. The glycerin concentration was unchanged during pregnancy. As with the post-partial group (0.53 mg/100 ml) the values were lower than those for the non-pregnant control group (1.14 mg/100 ml). The triglyceride concentration increased during pregnancy from 90.3 mg/100 ml to 179.7 mg/100 ml (2 alpha less than 0.00004, r = 0.6, n = 29). In the second and third trimesters (162.9 mg/100 ml, 179.7 mg/100 ml) and post partum (162.3 mg/100 ml) the values were higher than that for the non-pregnant controls (101.5 mg/100 ml). (ABSTRACT TRUNCATED AT 250 WORDS)

Insulin binding to erythrocytes before and after changing from porcine to biosynthetic human insulin in children with type-I diabetes.

The binding of [125I]insulin to isolated erythrocytes from diabetic children (n = 27) before (group a) as well as one and five months after changing from porcine to biosynthetic human insulin (groups b and c) was investigated. An analysis of variance of the binding parameters, determined by a nonlinear regression procedure, yielded statistically significant differences between the receptor affinities Ka as well as between the receptor concentrations Xo of the groups a and b, a and c and b and c. (formula: see text). The results suggest that the change from porcine insulin to biosynthetic human insulin induces a short-term as well as long-term increase in the affinity, and a decrease in the concentration of the erythrocyte insulin receptors.

Insulin binding to erythrocytes in children with type-I diabetes mellitus.

Specific binding of [125I]insulin to isolated erythrocytes was investigated in four groups of children (A) Healthy children under 10 years of age (n = 20) (B) Healthy children over 10 years of age (n = 13) (C) Diabetic children under 10 years of age (n = 12) (D) Diabetic children over 10 years of age (n = 63). In addition, all diabetic children (n = 75) were subdivided into four groups according to the duration of diabetes. (E) less than 2 years, (F) 2--4 years, (G) 4--6 years, and (H) greater than 6 years. By means of a nonlinear regression analysis for the extraction of binding parameters (assuming a single receptor class model with independent receptor sites) and methods of variance analysis, statistically significant differences were observed for the receptor affinities Ka (10(8) l/mol) and the receptor concentrations X0 (nmol/l) between groups A and C, B and D, C and D, but not between A and B. The affinities of groups C and D were found to be higher than the corresponding values of groups A and B, whereas the receptor concentrations exhibited an inverse behaviour. A significant increase of the receptor concentration and decrease of the receptor affinity depending on the duration of diabetes could only be proved to exist during the first 2 years of the disease.

[Diabetes specific hand changes (cheiropathy) in children and adolescents with insulin-dependent diabetes (type I)]. / Diabetesspezifische Handveränderungen (Cheiropathie) bei Kindern und Jugendlichen mit insulinbedürftigem Diabetes (Typ I).

215 children and adolescents with insulin dependent diabetes (age: 12(6)/12 +/- 3(9)/12 yrs; duration of diabetes 4(5)/12 +/- 3(9)/12 yrs, daily insulin requirement: 0.74 +/- 0.26 I.U./kg b.w.) were investigated for the presence of hand changes (cheiropathy) due to diabetes. Controls were 110 healthy persons of similar age (age: 11(5)/12 +/- 4(8)/12 yrs). Signs of cheiropathy were found in 44 (20.5%) of the diabetics. In 28 of these diabetics reduced mobility of the proximal and/or distal interphalangeal joints of one finger and in 16 others of at least two fingers was observed. No pathological alterations were found in the wrists, shoulder joints or spine. Mild signs of cheiropathy were seen in 5 (4.5%) of the controls. A significant positive relationship was found between age and duration of diabetes and the severity of cheiropathy. Diabetics with cheiropathy also had significantly higher daily insulin requirements than others. Of 49 patients with good diabetic control only one (2.0%) had signs of cheiropathy. In the group of 82 diabetics with fair control 12 (14.6%) showed hand changes, in the group of 84 patients with poor control 31 (36.9%). Cheiropathy must be considered to be a prognostic indicator of impending microangiopathy (retinopathy, nephropathy and neuropathy) in diabetic children and adolescents.

[Diabetes-specific hand changes in type I diabetes mellitus]. / Diabetes-spezifische Handveränderungen bei Diabetes mellitus vom Typ I.

Diabetes-specific hand alterations (cheirarthropathy) were observed in 44 out of a total of 215 children and adolescents with insulin-dependent diabetes. In 28 of them limitations of movement in the proximal or (and) distal interphalangeal joints of one finger, and in the remaining 16 patients changes of at least two fingers were seen. Hand and shoulder joints or the vertebral column were not affected. In a control group of 110 probands without metabolic disorder only five showed cheirarthropathy. The frequency of diabetes-specific alterations of the hand increased with the age of the patients, the duration of diabetes and insulin requirements. In particular, the quality of metabolic control is of paramount importance for the as yet unclear pathogenesis of cheirarthropathy.

Insulin binding to erythrocytes from pregnant, postpartum, follicular and luteal states.

Specific binding of [125I] insulin to isolate erythrocytes from four groups of women was investigated: (A) pregnant subjects between weeks 38 and 40 of pregnancy (n = 18), (B) postpartum subjects within 6 days after delivery (n = 20), (C) normal women during the follicular phase of the menstrual cycle (n = 12) and (D) normal women during the luteal phase of the menstrual cycle (N = 11). Specific [125I] insulin binding (fraction), fasting plasma glucose concentrations (mmol/l) and the corresponding insulin concentrations (mU/l) were 0.074 +/- 0.012 / 4.00 +/- 0.58 / 29.4 +/- 21.4 for group A, 0.065 +/- 0.016 / 4.40 +/- 0.75 / 41.5 +/- 26.2 for group B, 0.052 +/- 0.008 / 4.58 +/- 0.62 / 6.7 +/- 4.0 for group C and 0.054 +/- 0.011 / 4.49 +/- 0.63 / 8.3 +/- 5.9 for group D. By using a modified Scatchard analysis, statistically significant differences were observed between the receptor affinities of the groups A and D, B and D, A and C. The receptor affinities and concentrations were not significantly different between the follicular and the luteal phases. From the data, no inverse correlation between the plasma insulin concentration and receptor binding was seen, i.e. the phenomenon of downregulation of insulin receptor concentration with hyperinsulinaemia seemed not to apply to erythrocytes.

[C-peptide excretion in 24 hours-urine as an indicator of B-cell residual function in children and adolescents with type-I-diabetes (author's transl)]. / Die C-Peptidausscheidung im 24 Std-Urin als Indikator der B-Zell-Residualfunktion bei Kindern und Jugendlichen mit Typ-I-Diabetes.

In 140 juvenile diabetics residual B-cell-function was measured according to the amount of the immunoreactive C-peptide (IRCP) in the 24 h-urine. We were able to repeat this test after two years in 69 of these patients. All diabetic children showed maintained residual insulin secretion (mean +/- S mean 2.60 +/- 0.31 nmol/24 h). There was a significant negative relationship (p less than 0.001) between the duration of diabetes and the extend of the residual B-cell-function. C-peptide urine excretion of the diabetics who were followed up dropped significantly (0.08 down to 0.02 nmol/kg/24 h, p less than 0.001), and the daily insulin requirement increased significantly (0.36 to 0.67 U/kg, p less than 0.05). In comparison, children with a shorter duration of the diabetes (less than 3 years) showed a more rapid decrease of their residual B-cell function with a simultaneously greater increase of the daily insulin dose as opposed to children with the diabetes for longer than 3 years at the time when they were first seen. With a short course of diabetes the decrease of the C-peptide and the increase of the daily insulin dose were negatively correlated (p less than 0.001). The clinical phenomena of the remission period as known until now are related to the decline of B-cell function.

[Influence of benzbromarone on the pharmacokinetics and pharmacodynamics of oxipurinol]. / Der Einfluss von Benzbromaron auf Pharmakokinetik und Pharmakodynamik von Oxipurinol.

1. When giving 100 mg allopurinol and 20 mg benzbromarone in a fixed combination we found that the oxipurinol levels differed at 0 and after 4 h from those after administration of 100 mg allopurinol; the oxipurinol clearance is increased; benzbromarone increased the glomerular filtration rate as well as the urine volume. 2. The urate serum levels are decreased under additional administration of benzbromarone, the urate clearance is increased; urate levels in serum dropped slower than under monotherapy with alloprinol and increased again within the last 12 h.

Rapid radioimmunoassay for insulin and its application in localizing occult insulinomas by intraoperative pancreatic vein catheterization.

A rapid RIA for insulin and its application to localising occult insulinomas during surgical exploration is described. A standard curve and twelve serum samples can be assayed within 45 min. The assay is equivalent with respect to accuracy and precision to conventional RIAs for insulin. Pancreatic vein catheterisation at laparotomy and immediate insulin determination made it possible to localize and resect two insulinomas which were not demonstrated by arteriography, computed tomography, ultrasound, and not palpable at surgery. We suggest that the new technique will end the long controversy concerning subsequent management of occult insulinomas.