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Biomedical subjects

C Kühl

Publications and source records attributed to C Kühl.

At least 37 records · Page 2Linked to original sources
PubMed1990

Mechanism of action of oral contraceptives on carbohydrate metabolism at the cellular level.

Although the available scientific data on the undesired metabolic effects of sex steroids have accumulated rapidly, most are of a descriptive nature, and only a few studies elucidate the impact at the cellular level and the possible interrelationship between different metabolic systems. This review summarizes the influence of different contraceptive steroid combinations on glucose metabolism and points to the possible mechanisms behind a disturbance of the euglycemic homeostasis with a concomitant change in lipid metabolism. Today the general concept is that the influence of combined sex steroid products on glucose metabolism is mainly caused by the progestogen components, although artificial estrogens may act synergistically. The diabetogenic effects of the progestogens make it important to consider the development during the last decade of the new more selective progestogens of the gonane type. From recent studies it seems, however, that intake of contraceptive combinations of ethinyl estradiol in combination with these types of gonanes, such as desogestrel and gestodene, may also be accompanied by increased insulin resistance, specifically, a hyperinsulinemic response to a glucose challenge despite unchanged glucose values compared with a baseline test. This is similar to observations made with combinations of ethinyl estradiol and other more traditional types of progestogens of the gonane and estrane type. It is conceivable that the diabetogenic effects of the progestogens are caused by a change in insulin receptor binding or a postreceptor defect in the cellular insulin action. The clinical implications of the diabetogenic effects of the sex steroids are hard to interpret, but more long-term exposure of arterial tissue to elevated concentrations of glucose and insulin results in inhibition of lipolysis and synthesis of cholesterol and triglycerides, which result in the development of lipid-filled lesions--fatty streaks--similar to those of early atherosclerosis.

Blood Glucose↗
PubMed1990

T-lymphocyte subpopulations in pregnant women with newly diagnosed type 1 diabetes.

The thymus-dependent immune system is involved in the disease process underlying Type 1 diabetes. Several studies have thus shown the distribution of peripheral T-lymphocyte subsets to be altered in diabetics. Unlike many other autoimmune diseases which improve during pregnancy, Type 1 diabetes has a higher incidence in pregnant than in non-pregnant women. Therefore, in this study the distribution of lymphocyte subpopulations in the blood was examined in pregnant, newly diagnosed Type 1 diabetic patients and compared with values from non-pregnant patients and healthy controls. The pregnant diabetics displayed a higher percentage of CD8+ cells (28.4 +/- 1.2%) than the non-pregnant diabetics (21.6 +/- 1.3%, p less than 0.005), but did not differ from the controls (29.0 +/- 1.3%). The CD3+ and CD4+ cell distribution displayed no significant difference within the groups. Among the pregnant diabetics a positive correlation was found between the percentage of CD4+ cells and the week of pregnancy when diabetes was diagnosed (p less than 0.01). No other correlations between immunological and clinical parameters were found. Thus the subsets of immune cells are not changed in an autoimmune direction for pregnant, newly diagnosed Type 1 diabetics as they are for non-pregnant. Therefore, the increased incidence of Type 1 diabetes in pregnant women is unlikely to be due to intensified autoimmune alterations in the immune system, but rather to changes induced in the beta-cells during pregnancy as discussed.

Adult↗
PubMed1989

Activity of enzymes of glucose and triglyceride metabolism in adipose and muscle tissue from normal pregnant women at term.

In order to further investigate insulin insensitivity in pregnancy, the activities of key enzymes in glycolysis and lipid metabolism were measured in adipose and muscle tissue biopsies from 20 normal pregnant women undergoing caesarean section at term, and 23 non-pregnant women of similar age and body weight undergoing gynaecological surgery. The activity of pyruvate kinase was decreased in pregnant women in both adipose tissue (0.015 (0.009-0.024) (median and range) vs 0.020 (0.009-0.038) Ug-1 wet weight, p less than 0.05) and muscle tissue (6.7 (3.6-10.9) vs 12.0 (2.8-16.2) U g-1 wet weight, p less than 0.001). The activity of hexokinase was decreased in adipose tissue only (0.045 (0.022-0.085) vs 0.057 (0.025-0.097) U g-1 wet weight, p less than 0.05), while the activity of phosphofructokinase was decreased in muscle tissue only (1.3 (0.7-2.6) vs 2.1 (0.3-4.5) U g-1 wet weight, p less than 0.01). Glucose-6-phosphate dehydrogenase activity was increased in muscle tissue (0.30 (0.11-0.59) vs 0.17 (0.09-0.48) U g-1 wet weight, p less than 0.05), while the activity of hydroxyacyl-CoA dehydrogenase was decreased in adipose tissue (0.5 (0.3-1.1) vs 1.0 (0.5-2.3) U g-1 wet weight p less than 0.001) from the pregnant women. Similar results were found when enzyme activities were calculated per gram of protein, but with poorer reproducibility.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed1988

Adipocyte insulin receptor binding and lipogenesis at term in normal pregnancy.

Lipogenesis in subcutaneous abdominal adipocytes during late human pregnancy was investigated by studying insulin receptor binding, 3-O-methyl-(14C-(U]-glucose flux and incorporation of (14C(U]-glucose into CO2 (oxidation) and total lipids (lipogenesis) in adipocytes from 18 health pregnant women undergoing Caesarean section at term, and 19 non-pregnant women undergoing gynaecological surgery. The cell diameter and fasting insulin were increased in the pregnant women, compared with controls (P less than 0.01 and P less than 0.05, respectively). The insulin receptor binding, 3-O-methyl-glucose flux, and basal oxidation were similar in both groups. Basal lipogenesis was higher in adipocytes from pregnant women than from controls (P less than 0.05), but the maximally stimulated increment was similar in both groups. Basal and maximally stimulated lipogenesis correlated positively with the cell diameter (P less than 0.001 and P less than 0.05, respectively). The findings indicate that lipogenesis in subcutaneous abdominal adipocytes from pregnant women is increased due to post-receptor events and that adipocytes do not contribute to the insulin resistance in late pregnancy.

Adipose Tissue↗
PubMed1988

Comparison of continuous subcutaneous insulin infusion with multiple insulin injections using the NovoPen.

Twenty-one patients with insulin-dependent diabetes mellitus (IDDM) participated in a 20-week randomized cross-over comparison of continuous subcutaneous insulin infusion (CSII) with intensified conventional treatment (ICT) using the NovoPen. The Medix or the Auto-Syringe pumps were used for CSII and, during ICT with NovoPen, conventional plastic syringes were used for injections of intermediate-acting insulin at bedtime. At entry HbA1c, was 8.7 +/- 0.4% (mean +/- SE) in CSII patients and 8.8 +/- 0.5% in the ICF group. HbA1c declined significantly in both groups (ICT 7.6 +/- 0.2%; CSII 7.6 +/- 0.2%) though there was no significant difference between the responses. Overall mean blood glucose was slightly but significantly lower during CSII than during ICT (CSII: 7.6 +/- 0.2 mmol/l; ICT: 8.7 +/- 0.4 mmol/l, p less than 0.05). The number of hypoglycaemic episodes did not differ significantly between patients treated with NovoPen and CSII. At the end of the study, a questionnaire revealed that all but one patient preferred ICT with NovoPen to conventional therapy. Given the choice for future treatment, 6 patients chose CSII, 12 patients preferred ICT with NovoPen and 1 was unsure.

Adult↗
PubMed1988

Comparative trial of the effects on glucose tolerance and lipoprotein metabolism of two new oral contraceptives containing gestoden and desogestrel.

The effects of two new low-dose oral contraceptives (triphasic ethinyl estradiol/gestoden and monophasic ethinyl estradiol/desogestrel) on glucose tolerance, plasma insulin response to glucose, fasting plasma cortisol, triglycerides (TG), total cholesterol (C), HDL-C, LDL-C, VLDL-C and sex hormone binding globulin (SHBG) were investigated in two groups of healthy women (n = 10). Investigations were performed prior to hormone ingestion and after treatment for 2 and 6 months. In both groups, fasting plasma levels of glucose and insulin as well as the areas below the glucose concentration curves were unchanged during treatment, whereas the insulin response to oral glucose was equally increased (p less than 0.05). Intake of both compounds was followed by similar increases in the levels of HDL-C (p less than 0.05) and in the HDL-C/total-C (p less than 0.05). A transient decrease in the levels of LDL-C was observed in both groups after two months. During intake of the gestoden-containing compound increases in VLDL-C and TG levels were registered after six months (p less than 0.05). Plasma levels of SHBG increased similarly in both groups (p less than 0.01). The study indicates, that intake of both hormonal compounds is free from adverse effects on glucose tolerance and lipoprotein metabolism known to be of clinical significance. No differences in the metabolic effects were found between the two compounds.

Adult↗
PubMed1987

Insulin bolus given by sprinkler needle: effect on absorption and glycaemic response to a meal.

Two studies were conducted investigating the effect of injecting short acting insulin subcutaneously by means of a sprinkler needle; this needle has 14 small holes in the wall but is sealed at the tip. In the first study absorption of 8 U iodine-125 labelled Actrapid HM injected subcutaneously at two separate sites in the abdominal wall was measured in 10 patients. One injection was given with the sprinkler needle and the other with a conventional needle. The initial dose absorbed during the first 30 minutes was significantly higher with the sprinkler needle. In the second study 10 U Actrapid HM was given to 11 other patients (all negative for C peptide and with low insulin binding antibody titres) on two separate days immediately before a standardised breakfast either by the sprinkler needle or by a conventional needle (random order). Plasma free insulin increased more rapidly and to higher concentrations with the sprinkler needle and the glycaemic response was considerably diminished. The sprinkler needle improves both the insulin absorption rate and the glycaemic response to a meal and may reduce the 30 minutes or so before meals that diabetics must inject to minimise postprandial hyperglycaemia.

Absorption↗
PubMed1987

Increased incidence of true type I diabetes acquired during pregnancy.

A longitudinal study was carried out of all patients with newly acquired insulin dependent diabetes during pregnancy (as distinct from non-insulin-dependent gestational diabetes) seen at the Copenhagen Centre for Diabetes and Pregnancy during 1966 to 1980. The series comprised 63 patients with a mean age of 27 (SEM 1) years. At diagnosis the mean fasting blood glucose concentration was 15.6 (1.3) mmol/l and mean maximal insulin dose 49 (3) IU/day. At a prospective follow up examination a mean of 8 (SEM 1) years after diagnosis 46 of 60 patients (77%) were being treated with insulin (35 (2) IU/day) and had a very low mean stimulated plasma C peptide value (0.12 (0.02) nmol/l) suggesting absent or nearly absent beta cell function. The remaining 14 patients (23%), not currently receiving insulin, appeared to be severely glucose intolerant, having a mean fasting blood glucose concentration of 13.4 (1.2) mmol/l. Thus most of these patients developing insulin dependent diabetes during pregnancy had true type I disease. Compared with the age specific incidence of type I diabetes in the background population of women the incidence was at least 70% higher in pregnant than non-pregnant women (p less than 0.001; chi 2 = 11.6; f = 1). This increased incidence occurred in the third trimester when the risk of developing type I diabetes was 3.8 times that of non-pregnant women (p less than 0.000001; chi 2 = 35.6; f = 1). Finally, the risk of developing insulin dependent diabetes during pregnancy was lower when conception occurred in the winter (p less than 0.05; chi 2 = 4.18; f = 1).

Adult↗
PubMed1987

Effect of porcine gastric inhibitory polypeptide on beta-cell function in type I and type II diabetes mellitus.

The effect of highly purified natural porcine GIP on C-peptide release was examined in six type I (insulin-dependent) diabetics (IDD) with residual beta-cell function, six type II non-insulin-dependent) diabetics (NIDD), and six normal subjects. All subjects were normal weight. From -120 minutes to 180 minutes glucose or insulin was infused IV to achieve a constant plasma glucose level of 8 mmol/L. On two separate days GIP (2 pmol/kg/min) or isotonic NaCl at random were infused from 0 to 30 minutes. After 10 minutes of GIP infusion plasma IR-GIP concentrations were in the physiologic postprandial range. At 30 minutes a further increase in IR-GIP to supraphysiologic levels occurred. In all subjects plasma, C-peptide increased more after 10 minutes of GIP infusion (IDD, 0.48 +/- 0.05; NIDD, 0.79 +/- 0.11; normal subjects, 2.27 +/- 0.29 nmol/L) than on the corresponding day with NaCl infusion (IDD, 0.35 +/- 0.03; NIDD, 0.62 +/- 0.08; normal subjects, 1.22 +/- 0.13 nmol/L, P less than .05 for all). The responses of the diabetics were significantly lower than that of the normal subjects (P less than .001 for both groups). No further increase in C-peptide occurred during the remaining 20 minutes of the GIP infusion in the diabetic subjects (IDD, 0.49 +/- 0.05; NIDD, 0.83 +/- 0.10 nmol/L). In the presence of a plasma glucose concentration of 8 mmol/L, physiologic concentrations of porcine GIP caused an immediate but impaired beta-cell response in IDD and NIDD patients.

Adult↗
PubMed1987

Outcome of the glucagon test depends upon the prevailing blood glucose concentration in type I (insulin-dependent) diabetic patients.

The outcome of 97 paired glucagon and meal tests was related to the prevailing fasting blood glucose concentrations on the two test days. At blood glucose concentration less than 7 mmol/l both the C-peptide responses and the maximal (6 min) C-peptide concentrations during the glucagon tests were significantly lower than the corresponding values found during the meal tests. During the glucagon tests, a direct relationship was found between the responsiveness of the pancreatic beta-cells and fasting blood glucose values when these were between 3 and 7 mmol/l. No significant difference was found between the outcome of the two tests when the fasting blood glucose concentration was greater than 7 mmol/l. The results indicate that the outcome of the glucagon test in Type I patients depends upon the prevailing fasting blood glucose concentration and that the predictive value of the glucagon test as to how the beta-cells will respond to a meal during everyday life is low when fasting blood glucose is less than 7 mmol/l.

Adult↗
PubMed1987

Oral contraception and insulin sensitivity: in vivo assessment in normal women and women with previous gestational diabetes.

The sensitivity to insulin (euglycemic clamp technique) was assessed in previous gestational diabetic women (n = 6) and nondiabetic women (n = 6) before and twice during low-dose triphasic oral contraceptive administration (ethinyl estradiol and levonorgestrel) for 6 months. Both groups had normal plasma glucose and insulin levels during oral glucose tolerance tests before and during treatment. In vivo peripheral insulin action was measured during insulin infusion of 40 mU/m2 X min with plasma glucose clamped at fasting levels. Before treatment glucose infusion rates were identical in both groups [1.56 +/- 0.12 (SEM) mmol/m2 X min and 1.51 +/- 0.09 mmol/m2 X min, respectively]. After hormonal treatment for 6 months the amount of glucose infused decreased significantly in the previously gestational diabetic women (1.10 +/- 0.12 mmol/m2 X min, P = 0.01), whereas the decrease was less pronounced in the nondiabetic women (1.30 +/- 0.22 mmol/m2 X min, P = 0.09). The decrease in insulin sensitivity was not sufficient to alter glucose tolerance either in the previous gestational diabetic women nor in the nondiabetic women.

Adult↗
PubMed1987

HLA associations in insulin-dependent diabetes mellitus diagnosed during pregnancy.

Sixty out of 63 patients with insulin-dependent diabetes mellitus (IDDM) diagnosed during pregnancy in the Diabetes Centre at the Department of Obstetrics and Gynaecology, Rigshospitalet, Copenhagen, were re-examined 2-16 years after diagnosis. Fourty-six patients were currently insulin-treated and the remaining 14 patients were all severely glucose intolerant. HLA-typing was carried out in 41 of these patients. The HLA phenotype distribution showed a highly significant difference from that of non-diabetics but was similar to that seen in IDDM not related to pregnancy. Thus, pregnancy may constitute a special trigger mechanism for IDDM, but the subsequent pathogenic mechanisms are probably the same as those involved in other cases of IDDM.

Diabetes Mellitus, Type 1↗
PubMed1987

Relationship between subcutaneous blood flow and absorption of lente type insulin.

To study the relationship between the absorption of intermediate acting insulin and the local subcutaneous blood flow (SBF) 8 diabetic patients were given subcutaneous injections of 125I labeled human lente type insulin and 133Xenon in the abdominal wall. External measurements of the tracer disappearance were performed and the insulin absorption rate and SBF were calculated. A curvilinear relationship between the insulin absorption rate and SBF was demonstrated with an initial almost linear relation but with decreasing impact of SBF when this was in the higher physiological range.

Absorption↗
PubMed1986

Obstetrical management in diabetic pregnancy: the Copenhagen experience.

The outcome of 223 pregnancies in Type 1 (insulin-dependent) diabetic women managed from 1981 to 1985 in the Centre for Pregnant Diabetics in Copenhagen is presented. There were 17 spontaneous and 9 induced abortions. The latter were all done on medical indications. Among the 201 infants weighing 1000 g or more (including 4 pairs of twins), three died perinatally, 2 with lethal congenital malformations and one was stillborn in the 32nd gestational week. This represents a perinatal mortality rate of 2 percent. Timing and mode of delivery is individualized, but the general scheme is to induce labour around the 38th week of pregnancy. It is emphasized that an increased risk of sudden intrauterine death still exists in late diabetic pregnancy.

Birth Weight↗
PubMed1986

Oral contraceptives and insulin receptor binding in normal women and those with previous gestational diabetes.

The effect of a low-dose triphasic oral contraceptive (ethinyl estradiol and levonorgestrel) on glucose tolerance, plasma insulin response to a glucose challenge, and insulin receptor binding to monocytes and erythrocytes was investigated in seven women with previous gestational diabetes and seven nondiabetic control subjects. Investigations were performed in the luteal phase before the hormonal intake and after hormonal treatment for 2 and 6 months. Before treatment, women with previous gestational diabetes had significantly impaired glucose tolerance (p less than 0.05) when compared with the healthy controls, but no differences in insulin receptor binding were observed. Glucose tolerance and the insulin response to oral glucose remained unchanged in both groups during the treatment period. In the control subjects a significant decrease (p less than 0.05) in insulin receptor binding to monocytes was observed after hormonal intake for 6 months whereas the insulin receptor binding remained unchanged in the women with previous gestational diabetes. No correlation was found between the receptor binding data obtained from monocytes and erythrocytes in either group of women. The study demonstrates that in lean nondiabetic women and women with previous gestational diabetes of normal weight without first-degree history of diabetes there is no apparent direct association between glucose tolerance, plasma insulin levels, and insulin binding to erythrocytes and monocytes during intake of low-dose oral contraceptives.

Adolescent↗