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C Kühl

Publications and source records attributed to C Kühl.

At least 19 recordsLinked to original sources
PubMed2001

N-tert-Butyl-N'-(5,7-dimethyl-1,8-naphthyridin-2-yl)urea.

The title compound, C(15)H(20)N(4)O, has been synthesized as an AADD recognition unit for quadruple hydrogen bonds. All non-H atoms of the molecule apart from two methyl groups of the tert-butyl group lie in a common plane. An intramolecular hydrogen bond is formed connecting two N atoms. In the solid state, the title compound crystallizes as a centrosymmetric dimer connected by N-H...O=C interactions with an N...O distance of 2.824 (2) A.

Journal Article↗
PubMed1998

Etiology and pathogenesis of gestational diabetes.

A significant amount of information regarding the pathogenesis of gestational diabetes mellitus (GDM) has been gathered since the Third Workshop-Conference on GDM. In spite of this, it is still not known why GDM develops in 2-3% of all pregnant women. Similar frequencies of HLA-DR2, DR3, and DR4 antigens in healthy pregnant women and women with GDM and low prevalences of markers for autoimmune destruction of the beta-cells in GDM pregnancy rule out the possibility that GDM is a disease of autoimmune origin. Insulin secretion during an oral glucose tolerance test (OGTT) or a meal is substantially increased in women with GDM compared with the same women postpartum. However, insulin secretion increases less in women with GDM than in pregnant women who retain normal glucose tolerance (NGT). Peak insulin concentrations during an OGTT occur later in women with GDM, and following intravenous glucose, a reduced first-phase insulin response is also seen in these women. Second-phase insulin responses are similar in pregnant women with NGT and GDM. Excessive secretion of proinsulin, which does not always return to normal postpartum, is often observed in women with GDM. It is conceivable that this might reflect a stress on the beta-cells and that the beta-cells are stressed because they try to counter the decreased insulin sensitivity that develops during pregnancy. Thus, insulin sensitivity decreases by 50-70% in both normal and GDM pregnancy, but whereas insulin sensitivity returns to normal postpartum in pregnant women with NGT, this is not always the case in GDM. Insulin receptor binding to target tissues is largely unaffected by normal and GDM pregnancy; the same is true for basal and insulin-stimulated insulin receptor-bound tyrosine kinase activity. There is indication that certain post-insulin-insulin receptor binding events are altered in tissues from women with GDM. However, data are still scarce, and more studies are needed before the intracellular events leading to a decreased insulin sensitivity have been resolved. Hormones that circulate in high concentrations in pregnancy (e.g., progesterone, cortisol, prolactin, human placental lactogen, and estrogen) have all been shown, in animal models, to be able to influence beta-cell function and/or the peripheral tissue sensitivity to insulin, but whether they play similar roles in human pregnancy remains to be investigated.

Diabetes, Gestational↗
PubMed1996

GAD65 autoantibodies in women with gestational or insulin dependent diabetes mellitus diagnosed during pregnancy.

We have studied the presence of GAD65 autoantibodies in women with insulin-dependent diabetes mellitus (IDDM) (n = 28) or gestational diabetes (GDM) (n = 139) diagnosed during pregnancy and investigated the temporal relationship between these autoantibodies and the subsequent recurrence or development of IDDM. Among the GDM patients, 4.3% (6 of 139) developed true IDDM during a median follow-up period of 6.3 years (range 4.0-11.0). Of these, 2.2% (3 of 139) were positive for GAD65 autoantibodies at diagnosis of GDM compared to 0% (0 of 27) of healthy pregnant women. All 3 GAD65 autoantibody positive GDM patients subsequently developed IDDM after a median of 14 months (range 4-34). GAD65 autoantibodies were present in 50% (14 of 28) of sera from women with IDDM diagnosed during pregnancy. The non-insulin-requiring remission period was significantly shorter in GAD65 autoantibody positive patients (median 0.5 years [range 0-6.0 years]) than in GAD65 antibody negative patients (median 2.6 years; range 0-9.7 years; p < 0.05). The results suggest that screening for GAD65 autoantibodies in women with GDM or IDDM diagnosed during pregnancy may be useful for predicting the clinical course of the disease.

Adolescent↗
PubMed1996

Impaired insulin-stimulated nonoxidative glucose metabolism in glucose-tolerant women with previous gestational diabetes.

OBJECTIVE: Our purpose was to investigate insulin sensitivity and insulin secretion in women with previous gestational diabetes. STUDY DESIGN: Twelve women with previous gestational diabetes and 11 controls were examined by oral and intravenous glucose tolerance tests and a hyperinsulinemic euglycemic clamp including indirect calorimetry. All women were lean and had normal oral glucose tolerance test results. Activities of glycogen synthase, phosphofructokinase, and hexokinase were measured in vastus lateralis muscle biopsy specimens obtained in the basal state and after insulin stimulation. RESULTS: Women with previous gestational diabetes had a decreased glucose disposal rate (p<0.01) because of a reduced insulin-stimulated nonoxidative glucose metabolism (6.63 +/- 0.47 vs 9.04 +/- 0.57 mg/kg fat-free mass per minute, p<0.01). The muscle activities of glycogen synthase, phosphofructokinase, and hexokinase were similar in the two groups. The first-phase insulin response to the intravenous glucose tolerance test was, in absolute terms, comparable in the two groups. However, when the decreased insulin sensitivity was taken into account, women with previous gestational diabetes had a relative insulin secretion deficiency. CONCLUSION: Women with previous gestational diabetes have a decreased insulin sensitivity and a relative impairment of insulin secretion.

Adult↗
PubMed1995

A longitudinal study of plasma insulin and glucagon in women with previous gestational diabetes.

OBJECTIVE: To investigate whether plasma insulin or glucagon predicts later development of diabetes in women with gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS: The subjects studied were 91 women with diet-treated GDM and 33 healthy women. Plasma insulin and glucagon during a 50-g oral glucose tolerance test (OGTT) were measured during pregnancy, postpartum, and at follow-up 5-11 years later. At follow-up, the women were also examined with a 75-g OGTT or an intravenous glucagon test. RESULTS: Twenty-seven (30%) of the women with previous GDM had abnormal glucose tolerance at follow-up (2 had insulin-dependent diabetes mellitus, 13 had non-insulin-dependent diabetes mellitus, and 12 had impaired glucose tolerance). Compared with the control subjects, women with previous GDM had relatively impaired insulin secretion (decreased insulinogenic index and delayed peak insulin response) at all time points investigated; this was also found when only nonobese glucose-tolerant women were examined. Low insulin secretion during pregnancy together with a high fasting plasma glucose level at the diagnostic OGTT in pregnancy and hyperglycemia during the postpartum OGTT were predictive for subsequent development of overt diabetes (logistic regression analysis). CONCLUSIONS: Women who develop GDM have a relative insulin secretion deficiency, the severity of which is predictive for later development of diabetes. Furthermore, our data indicate that their relatively reduced beta-cell function may be a significant pathogenic factor in relation to the high incidence of subsequent diabetes in women with GDM. This could be important in the design of follow-up programs for women with previous GDM.

Adult↗
PubMed1994

Prevalence and predictive value of islet cell antibodies and insulin autoantibodies in women with gestational diabetes.

The objective of the present study was to investigate the predictive value of islet cell antibodies (ICA) and insulin autoantibodies (IAA) for development of diabetes in women with previous gestational diabetes (GDM). Two hundred and forty-one previous diet-treated GDM patients and 57 women without previous GDM were examined 2-11 years after the index pregnancy. In subgroups, plasma from the diagnostic OGTT during index pregnancy was analysed for ICA and IAA. Among the previous GDM patients, 3.7% had developed Type 1 diabetes and 13.7% Type 2 diabetes. Four (2.9%) of the 139 GDM patients tested for ICA were ICA-positive and three of these had Type 1 diabetes at follow-up, as well as three ICA-negative patients. The sensitivity, specificity, and predictive value of ICA-positivity for later development of diabetes were 50%, 99%, and 75%, respectively. None of the women was IAA-positive during pregnancy. In conclusion, the majority of the patients with GDM did not show evidence of ongoing autoimmune destruction of the beta cells during the index pregnancy. However, ICA-positive GDM patients had a high risk of developing Type 1 diabetes later in life.

Autoantibodies↗
PubMed1993

Insulin receptor binding and tyrosine kinase activity in skeletal muscle from normal pregnant women and women with gestational diabetes.

OBJECTIVE: To ascertain whether the decreased glucose tolerance and insulin resistance found in normal and gestational diabetic pregnancy might be associated with changes in insulin receptor function. METHODS: Eight nonpregnant healthy women (nonpregnant controls), eight healthy pregnant women (pregnant controls), and eight women with gestational diabetes were investigated. All were non-obese. Muscle biopsies were obtained from the vastus lateralis muscle, and insulin binding and tyrosine kinase activities in partially purified skeletal muscle insulin receptors were studied. The pregnant controls were investigated in late pregnancy, and the women with gestational diabetes were investigated at the time of diagnosis of gestational diabetes. A further examination was carried out 2 months after delivery. RESULTS: Insulin binding at tracer insulin concentration (60 pmol/L) was diminished in women with gestational diabetes compared to nonpregnant controls (P < .05), whereas normal pregnant women did not differ from the other two groups. Postpartum, no differences in insulin binding were found between the groups. Basal and maximal tyrosine kinase activities toward the exogenous substrate poly(Glu4Tyr1) were the same in nonpregnant controls, pregnant controls, and women with gestational diabetes. Postpartum, no differences in tyrosine kinase activity were found among the groups. Moreover, no significant differences in insulin binding or tyrosine kinase activity were found comparing pregnancy and postpartum values within the groups. CONCLUSION: The insulin resistance found in normal and gestational diabetic pregnancy is not likely to be caused by a defective insulin receptor tyrosine kinase, whereas decreased insulin receptor binding might have some pathogenic importance in gestational diabetes.

Adult↗
PubMed1992

Predictive factors for the development of diabetes in women with previous gestational diabetes mellitus.

OBJECTIVES: The purpose of this study was to determine the incidence of diabetes in women with previous dietary-treated gestational diabetes mellitus and to identify predictive factors for development of diabetes. STUDY DESIGN: Two to 11 years post partum, glucose tolerance was investigated in 241 women with previous dietary-treated gestational diabetes mellitus and 57 women without previous gestational diabetes mellitus (control group). RESULTS: Diabetes developed in 42 (17.4%) women with previous gestational diabetes mellitus (3.7% insulin-dependent diabetes mellitus and 13.7% non-insulin-dependent diabetes mellitus). Diabetes did not develop in any of the controls. Predictive factors for diabetes development were fasting glucose level at diagnosis (high glucose, high risk), preterm delivery, and an oral glucose tolerance test result that showed diabetes 2 months post partum. In a subgroup of previous patients with gestational diabetes mellitus in whom plasma insulin was measured during an oral glucose tolerance test in late pregnancy a low insulin response at diagnosis was found to be an independent predictive factor for diabetes development. CONCLUSIONS: Women with previous dietary-treated gestational diabetes mellitus have a considerably increased risk of later having diabetes. Follow-up investigations are therefore important, especially in those women with previous gestational diabetes mellitus in whom the identified predictive factors are present.

Adult↗
PubMed1991

Aetiology of gestational diabetes.

Glucose tolerance deteriorates in human pregnancy, but about 97-98% of all pregnant women retain a normal glucose tolerance and only 2-3% develop gestational diabetes. The data reviewed show that the diabetogenicity of pregnancy is not due to diminished secretion of insulin or disproportional secretion of proinsulin or glucagon, nor is an increased insulin degradation involved. Only quantitative differences in insulin secretion have been observed between normal pregnant women and women with gestational diabetes. The insulin responses to an oral glucose load or a test meal are thus lower in gestational diabetic women than in normal pregnant women, despite significantly higher plasma glucose concentrations in the gestational diabetics. Also the insulin responses to intravenous glucose injections or infusions are abnormal in gestational diabetics when compared with normal pregnant women, a difference which is still detectable for some time after the completion of pregnancy in at least a fraction of gestational diabetic women. There is thus ample evidence that the diabetogenicity of pregnancy is related to a pronounced peripheral resistance to insulin. The resistance is of a similar magnitude in normal pregnant women and women with gestational diabetes, and it does not seem to be caused by significant alterations in insulin receptor binding to target tissues. The insulin resistance of the whole body is increased to about three times that seen in the non-pregnant state. The increased resistance is caused by post-insulin receptor events and is probably brought about by the cellular effects of the increased plasma levels of one or more of the pregnancy-associated hormones and free cortisol. There is evidence that the resistance is predominantly located to the muscle tissue, where significant reductions in certain key enzymes in glucose and lipid metabolism have been demonstrated. Published evidence points to a similar degree of insulin resistance in normal pregnant women and normal weight women with gestational diabetes. Most normal pregnant women are able to counteract the peripheral resistance by a significant augmentation of their basal and nutrient-stimulated insulin secretion. However, a few (2-3%) of the women do not appear to have the capability to produce a sufficiently large increase in insulin secretion and hence cannot overcome the peripheral resistance. These are the women who become glucose intolerant to such an extent that the diagnostic criteria for gestational diabetes are fulfilled.

Diabetes, Gestational↗
PubMed1991

Glucose tolerance and incidence of pancreatic islet cell antibodies in pregnancy in women with thyroid autoantibodies.

The prevalence of pancreatic islet cell antibodies (ICA) and complement fixing ICA (CF-ICA) and the effect of pregnancy of glucose tolerance was studied in 3 groups of women. One group had thyroid autoantibodies in serum detected in early pregnancy and subsequent development of postpartum thyroiditis (PPT), another group had thyroid autoantibodies without signs of PPT and the third group did not have thyroid autoantibodies or PPT. In the women with thyroid autoantibodies and PPT, ICA were found in one of 12 women (8%, 95% confidence limits 0-38%). In the group with thyroid autoantibodies without PPT, ICA were found in three of 27 women (11%, 2-29%), whereas two of 20 women without thyroid autoantibodies had ICA (10%, 1-32%), N.S. Where present, serum ICA levels were very low and similar in early pregnancy and 6 months postpartum. CF-ICA were only found in two women with thyroid autoantibodies without signs of PPT. In all groups glucose tolerance was impaired in pregnancy when compared to postpartum despite an increased insulin response to glucose ingestion. In pregnancy, however, glucose tolerance was more impaired in the women with thyroid autoantibodies and subsequent PPT, than in the women without thyroid autoantibodies. Postpartum glucose tolerance was similar in all groups. It is concluded, that the presence of thyroid autoantibodies in early pregnancy or development of PPT is not accompanied by an increased prevalence of islet cell antibodies, but women with thyroid autoantibodies and subsequent PPT have a significantly more reduced glucose tolerance in late pregnancy than women without thyroid autoantibodies.

Adult↗
PubMed1991

Thyroid function and autoimmune manifestations in insulin-dependent diabetes mellitus during and after pregnancy.

Insulin-dependent diabetes is associated with other autoimmune diseases and subclinical hypothyroidism has been reported in pregnant diabetic women. We studied the thyroid function of 85 women with diabetes during pregnancy and after delivery, as well as various autoantibodies. During pregnancy, thyroid microsomal antibodies were present in 17/85, antibodies against thyroid peroxidase in 16/85, thyroglobulin antibodies in 2/85, parietal cell antibodies in 23/85, adrenal antibodies in 4/77, rheumatoid factor in 15/85, and thyroid-stimulating antibodies in 43/85. Presence of antibodies was not combined with thyroid dysfunction, but TSH and HbA1c was increased (p less than 0.005) in women with thyroid antibodies. The gestational age of the infants was lower (p less than 0.01) in women with positive thyroid-stimulating antibody titre, whereas the ponderal index was only lower in those with peroxidase antibodies (p less than 0.05). After delivery, microsomal and peroxidase antibodies were positive in 10 (17.5%) of 57 patients followed. Six women developed postpartum thyroiditis (10.5%), of whom 5 were positive for both microsomal and peroxidase antibodies; two of those showing a hyperthyroid phase also had positive thyroid-stimulating antibody titre. We conclude that autoantibodies occur with increased incidence in pregnant diabetic women. Thyroid antibodies are related to a slightly reduced thyroid capacity and involve a high risk of postpartum thyroiditis. Further, thyroid antibodies seem to influence the nutritional status of the infant.

Adult↗
PubMed1991

Insulin secretion and insulin resistance in pregnancy and GDM. Implications for diagnosis and management.

Glucose tolerance deteriorates in human pregnancy, but approximately 97-98% of all pregnant women retain a normal glucose tolerance, and only 2-3% develop gestational diabetes mellitus (GDM). Both nondiabetic pregnant women and women with GDM exhibit much higher insulin responses to oral or intravenous administration of glucose or amino acids than found in the nonpregnant state, and the insulin responses to a protein-rich meal are also significantly enhanced in pregnancy. Both quantitative and qualitative differences in insulin secretion exist between pregnant women with normal glucose tolerance (NGT) and women with GDM. Insulin responses to oral glucose and protein-rich meals are thus lower in pregnant women with GDM than in women with NGT, despite significantly higher mean plasma glucose concentrations in the women with GDM. Furthermore, peak plasma insulin concentrations occur later in women with GDM than in pregnant control subjects. Finally, a reduced first-phase insulin response to intravenous glucose can be observed in some women with GDM. Impairment of glucose tolerance in pregnancy is not related to a disproportional secretion of proinsulin nor is increased insulin degradation involved. These observations point to pregnancy as a state of peripheral insulin resistance. Because insulin-receptor binding is only slightly changed in pregnancy and not significantly different in pregnant women with NGT and women with GDM, it follows that the insulin resistance is located at the postreceptor level. Insulin-clamp and "minimal model" studies have shown that the whole-body insulin sensitivity is similarly reduced by about two-thirds of nonpregnant values in pregnant women with NGT and women with GDM.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1990

Type 1 (insulin-dependent) diabetes mellitus diagnosed during pregnancy: a clinical and prognostic study.

The study concerns the clinical outcome and later prognosis (regarding permanent insulin treatment) of patients who develop insulin-dependent diabetes mellitus during pregnancy (which is different from gestational diabetes). Sixty-three such patients (27 +/- 1 (SEM) years old) were delivered at the Copenhagen Centre for Diabetes and Pregnancy during the years 1966-1980. Obstetric complications such as toxaemia were seen in 9.5% of these study patients and the perinatal mortality was 6.3%, both percentages being higher than in the general population (1.1%, p less than 10(-7) and 1.0%, p less than 10(-3), respectively), but similar to those observed in patients with Type 1 diabetes diagnosed before pregnancy. In contrast, the frequency of malformations was 1.6%, the same as in the general population (1.4%), but lower than that seen in patients with long-standing diabetes (8.3%, p less than 0.05). At follow-up examination 8 +/- 1 years after diagnosis all patients were diabetic; 77% were insulin treated, having no or virtually no residual B-cell function, and were clearly Type 1 diabetic patients. After delivery 80% of the patients had a remission period (median 256 days) without insulin treatment. This remission period was absent or shortest in patients with the following characteristics (p less than or equal to 0.03): low age, first parity, not overweight, and high blood glucose level at diagnosis. These prognostic parameters should be considered in obligatory, clinical follow-up plans for such patients.

Adult↗