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Biomedical subjects

Monika Lechleitner

Publications and source records attributed to Monika Lechleitner.

34 records · Page 2Linked to original sources

The number of abnormal plasma glucose values in the oral glucose tolerance test and the feto-maternal outcome of pregnancy.

OBJECTIVE: With respect to the feto-maternal outcome of pregnancy both appropriate screening and treatment of gestational diabetes mellitus (GDM) remain a matter of debate. Furthermore, the importance of only one abnormal glucose value at the glucose tolerance test (GTT) is still discussed, including the term "gestational impaired glucose tolerance" with normal fasting but an increased 2h postprandial glucose value. STUDY DESIGN: We have evaluated the feto-maternal outcome of pregnancy in 152 women with abnormal glucose values during the oral 100g GTT. The data were analysed with respect to the number of abnormal GTT values and compared to age- and body mass index (BMI)-matched control groups including 304 women with normal GTT values. RESULTS: A positive family history of diabetes was found in 24.4% of the GDM women and in 16.4% of the control group. In 45.9% of the women with abnormal GTT values glucose target levels could be obtained by dietary management, 54.1% required additional insulin therapy. Insulin therapy was administered in 32.8% of the women with one abnormal GTT value, in 65.0% of the women with two abnormal values and in 83.3% of the women with three abnormal values. Compared to the age- and BMI-matched control group the percentage of women with hypertension was increased in women with one, two and three abnormal GTT values. The percentage of LGA and macrosomic infants was significantly increased only in women with three abnormal GTT values. Women with one, two or three abnormal GTT values revealed an increased percentage of caesarean section compared to the control group. CONCLUSIONS: Our results show that women with three abnormal GTT values are at an overall increased risk with respect to the feto-maternal outcome of pregnancy. Compared to the control group also women with only one abnormal GTT value revealed an increased risk indicating a need for further control and therapy.

Adult↗

Detection of a silent myocardial infarction with phosphor-31 two-dimensional chemical shift imaging (31P 2-D CSI).

BACKGROUND: Phosphor-31 two-dimensional chemical shift imaging (3lP 2-D CSI) is a well-established noninvasive technique in experimental research on regional myocardial ischemia, and it permits in vivo monitoring of high-energy phosphate metabolism in the myocardium without requiring external tracers,wherein phosphocreatinine (PCr) and beta-adenosine triphosphate (beta-ATP) are the main components of investigation. The decrease of PCr is one of the earliest reactions to acute myocardial ischemia, but also fixed defects after myocardial infarction (MI) showed a reduced ratio of PCr/beta-ATP, probably because of are modeling process taking place in the noninfarcted tissue. CASE REPORT: A 55-year-old patient with diabetes mellitus type 1 is reported, who presented within the scope of a study at the University Hospital Innsbruck, Austria, and in whom 31P 2-D CSI helped to detect a so far unknown coronary heart disease (CHD). CONCLUSION: In the presented case, 31P 2-D CSI for the first time helped to reveal a severe CHD and a so far unknown MI,and and if the calculated voxel size was chosen small enough, even a satisfying localization of the lesion became possible.

Adenosine Triphosphate↗

[Diabetes and lipids].

Dyslipidemia is one of the major cardiovascular risk factors especially for patients with type 2 diabetes mellitus. As a feature of the metabolic syndrome insulin resistance is also associated with an atherogenic lipoprotein phenotype. In type 1 diabetes inadequate glycemic control results in an increase of plasma triglyceride levels. The treatment of diabetic dyslipidemia is based on an improvement of glycemic control, in type 1 and type 2 diabetes, as well as in lifestyle recommendations, including dietary advice and physical exercise. The achievement of strict target levels, especially LDL-cholesterol values below 100 mg/dL, requires lipid lowering drug therapy. This LDL-cholesterol target level is based on the fact that diabetic patients reveal the same risk for myocardial infarction as non-diabetics after their first cardiovascular event. Thus the diagnosis of diabetes is regarded as an equivalent for manifest cardiovascular disease. The re-evaluation of large lipid intervention trials (4 S, CARE, LIPID, VA-HIT, Heart Protection Study) could clearly demonstrate also for the diabetic subpopulation that statin and fibrate therapy results in a significant reduction of the cardiovascular risk.

Anticholesteremic Agents↗

Effects of glimepiride on HbA(1c) and body weight in Type 2 diabetes: results of a 1.5-year follow-up study.

Sulphonylureas are effective and well tolerated in patients with Type 2 diabetes, but may be associated with weight gain, and lack of compliance due to multiple daily dosing. This open, uncontrolled surveillance study examined the efficacy and safety of glimepiride, a new sulphonylurea, administered once daily in patients with Type 2 diabetes. A total of 1,770 patients were enrolled in the study, and 284 patients were selected for follow-up. Patients received 0.5 to >4 mg glimepiride once daily for 1.5 years. HbA(1c) was reduced from 8.4% at baseline to 7.1% after 4 months and 6.9% after 1 and 1.5 years (median intra-individual change from baseline: -1.4, -1.5, and -1.7%, respectively; P<0.0001). Treatment with glimepiride also resulted in significant and stable weight loss relative to baseline, with the exception of patients with a body mass index of <25 kg/m(2). Mean body weight was reduced from 79.8 kg at baseline to 77.9 kg after 4 months, 77.2 kg after 1 year, and 76.9 kg after 1.5 years (mean intra-individual change from baseline: -1.9 kg, P<0.0001; -2.9 kg, P<0.05; -3.0 kg, P<0.005, respectively). Therefore, once daily glimepiride provides effective glycaemic control, and may have advantages over other sulphonylureas, because it exhibits weight neutralizing/reducing effects in patients with Type 2 diabetes.

Adult↗

The influence of obesity on the frequency and distribution of medication.

Obesity is a serious health problem in industrialized countries and is associated with a significant increase in total health care costs. Only few data are available about the costs of drug therapies in patients with an increased body weight treated under clinical routine procedures. Such data could support efforts to intensify obesity prevention and treatment programmes in order to reduce comorbidities and costs. We have evaluated body mass index (BMI), diagnosis, and medication in 3360 outpatients (2175 women and 1185 men; mean age: 56.7 +/- 17.5 years). All patients underwent physical examinations, including BMI determination, and provided a detailed record concerning medication. In 1809 patients, the percentage of body fat content was measured with a bioimpedance method (OMRON BF 302 body fat monitor). Continuous variables were compared using the t-test or Wilcoxon U-test. Frequency distributions were compared using chi-squared tests. With respect to BMI, most of the patients (n = 1793; 53 %) were overweight or obese, 1349 (40 %) showed a normal BMI and 218 (7 %) a low BMI. The majority of cardiovascular (61 %), rheumatological (61.1 %) and metabolic (60.4 %) medication was administered to overweight and obese patients. Parallel findings could be obtained by analysing the percentage of body fat and the frequency of medication. Overall, 82.5 % of all medication was given to patients with a body fat content >20 %. Our results support the importance of weight-reduction programmes in order to prevent an overall increase in the costs of medication as a consequence of overweight and obesity.

Anti-Obesity Agents↗

3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors improve myocardial high-energy phosphate metabolism in men.

PURPOSE: We intended to prove that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors or statins have a beneficial impact on the human myocardial, high-energy, phosphate metabolism. METHODS: The present study included 18 male patients (mean age 49.8 +/- 10.3) with statin-treated, familiar hypercholesterolemia (FH) and 13 male patients with untreated FH (mean age 44.6 +/- 9.5). Twenty-six healthy male volunteers served as controls (mean age 44.2 +/- 12.1). Phosphorus-31, two-dimensional chemical shift imaging (31P 2D CSI) of the heart was performed in all subjects using a 1.5 Tesla whole-body magnetic resonance (MR) scanner. The ratios between phosphocreatine (PCr) and beta-adenosine-triphosphate (beta-ATP) were calculated for the left ventricular myocardium. Furthermore, echocardiographic evaluation and stress tests were performed in all individuals. RESULTS: The untreated patients with FH exhibited a significant decrease in left ventricular PCr to beta-ATP ratios (1.78 +/- 0.34) compared with statin-treated FH patients (2.15 +/- 0.26, p < 0.001) and healthy controls (2.04 +/- 0.26, p = 0.009). The left ventricular PCr-to-beta-ATP ratios of the treated FH patients were in the range of the healthy controls. CONCLUSIONS: Our study shows for the first time an-improvement of the high-energy, phosphate metabolism in the left ventricular myocardium of patients with statin-treated FH compared with untreated FH patients.

Adenosine Triphosphate↗

Olanzapine induces insulin resistance: results from a prospective study.

BACKGROUND: The aim of this study was to compare glucose metabolism in patients with schizophrenia receiving olanzapine with that in control subjects. METHOD: We conducted a prospective, controlled, open study comparing body weight, fat mass, and indices of insulin resistance/ sensitivity in 10 olanzapine-treated patients with ICD-10 schizophrenia (olanzapine dose range, 7.5-20 mg/day) with those of a group of 10 mentally and physically healthy volunteers. Weight, fat mass, and indices of insulin resistance/sensitivity were assessed over individual 8-week observation periods from November 1997 to October 1999. RESULTS: Fasting serum glucose and fasting serum insulin increased significantly in the olanzapine-treated patients (p =.008 for glucose and p =.006 for insulin). The homeostasis model assessment (HOMA) index for beta cell function did not change significantly in the olanzapine-treated patients, whereas the HOMA index for insulin resistance did increase (p =.006). In the control group, these parameters were stable. A significant increase in body weight (p =.001) and body fat (p =.004) was seen in patients treated with olanzapine, while the control group showed no significant changes. CONCLUSION: This study indicates that the disturbances in glucose homeostasis during antipsychotic treatment with olanzapine are mainly due to insulin resistance. However, beta cell function remains unaltered in olanzapine-treated patients. We conclude that treatment with some second-generation antipsychotic drugs may lead to insulin resistance.

Adult↗

Austrian Moderate Altitude Study 2000 (AMAS 2000). The effects of moderate altitude (1,700 m) on cardiovascular and metabolic variables in patients with metabolic syndrome.

We investigated the changes in the cardiovascular system [resting blood pressure (BP) and heart rate (HR), measured by means of a 24-h ambulatory BP and a holter-electrocardiogram (ECG)], glycemic parameters, and lipid metabolism of subjects suffering from metabolic syndrome during a 3-week sojourn at 1,700 m in the Austrian Alps. A total of 22 male subjects with metabolic syndrome were selected. Baseline investigations were performed at Innsbruck (500 m above sea level). During the 3-week altitude stay the participants simulated a holiday with moderate sports activities. Examinations were performed on days 1, 4, 9, and 19. After returning to Innsbruck, post-altitude examinations were conducted after 7-10 days and 6-7 weeks, respectively. The 24-h ambulatory BP and holter ECG revealed a decrease in average HR, BP, and rate pressure product (RPP: systolic blood pressure x HR) after 3 weeks of altitude exposure. In some patients, an increase in premature ventricular beats was observed at the end compared to the beginning of the exposure to moderate altitude. The ECG revealed no ischemic ST-segment changes. Maximal physical capacity as measured by symptom-limited maximal cycle ergometry tests remained unchanged during the study. Six weeks after the altitude exposure the blood pressure increased again and returned to pretest levels. The Homeostasis Model Assessment index, which is a measure of insulin resistance, decreased significantly and glucose concentrations obtained after an oral glucose tolerance test were significantly lower after the stay at altitude compared to the basal values. We conclude that after a 3-week exposure to moderate altitude, patients with metabolic syndrome (1) tolerated their sojourn without any physical problems, (2) exhibited short-term favorable effects on the cardiovascular system, and (3) had significant improvements in glycemic parameters that were paralleled by a significant increase in high-density-lipoprotein-cholesterol.

Adaptation, Physiological↗

Effect of insulin therapy on endothelium-dependent dilation in type 2 diabetes mellitus.

Endothelial dysfunction is an early marker of atherosclerosis occurring in patients with type 2 diabetes mellitus. Endothelium-dependent dilation (EDD) has been shown to improve by combined therapy of insulin and metformin. Studies on endothelium-independent vasodilatory capacity, however, have had controversial results. We sought to investigate the vascular reactivity--EDD and endothelium-independent dilation--and their changes induced by the addition of insulin therapy to patients with type 2 diabetes mellitus pretreated with diet and oral hypoglycemic drugs. We therefore performed vascular studies in 21 poorly controlled type 2 diabetic patients and 11 nondiabetic control subjects by using high resolution ultrasound of the brachial artery. After 3 months of additional insulin therapy, vascular and laboratory measurements including C-reactive protein and parameters of glucose and lipoprotein metabolism were repeated. At baseline, EDD was significantly impaired in diabetic patients compared with controls (2.7 +/- 2.2% vs 7.0 +/- 1.8%, p <0.001), whereas endothelium-independent dilation was normal in both groups. After insulin therapy, EDD increased from 2.7 +/- 2.2% to 5.0 +/- 2.8% (p <0.001) in diabetic patients. All other vascular parameters did not change over the treatment period. The absolute change in EDD showed a significant negative correlation with the change in hemoglobin A(1c) (r = -0.67, p <0.001) and with fasting blood glucose (r = -0.84, p <0.001) levels. In contrast, there was no correlation between EDD and the observed changes in lipid and C-reactive protein levels. Our findings demonstrate that insulin therapy has beneficial effects on vascular function, resulting in enhanced EDD, most probably due to an improved glycemic control as the underlying mechanism.

Adult↗

Polycystic ovaries, obesity and insulin resistance in women with epilepsy. A comparative study of carbamazepine and valproic acid in 105 women.

In order to investigate the possible role of valproic acid therapy in the development of obesity, hyperinsulinism and polycystic ovaries (PCOs), we have studied metabolic parameters and ovarian morphology in epileptic women. A total of 105 women, who were treated for at least 2 years with valproate (n = 52) or carbamazepine monotherapy (n = 53), were included in the examination. Menstrual disturbances were reported by 29 (28 %) of the women, 12 (11 %) of the VPA treated women, and 17 (16 %) in the CBZ group. On ultrasound scan polycystic ovaries were found in 28 patients (27 %) of the whole study population, of whom 13 (12 %) received VPA and 15 (14 %) CBZ. The mean body mass index (BMI) was significantly higher in the VPA group (24.4 kg/m(2) +/- 4.1) than in CBZ treated patients (22.9 kg/m(2) +/- 2.4;p < 0.022), and serum triglycerides tended to be increased, while total cholesterol values (178.9 +/- 30.5) and LDL-cholesterol values (92.6 +/- 27.4) were significantly lower in the valproate group, than in the carbamazepine group (207.1 +/- 43.0 vs 115.1 +/- 42.0; p < 0.001). Postprandial insulin, C-peptide and proinsulin levels were significantly higher in VPA treated patients compared with those treated with CBZ, while no differences could be found in the fasting state. In conclusion we could thus demonstrate that the frequency of PCOs in 27 % of epileptic women seems to be similar to that in the general population with a frequency of 20-30 %. The development of PCOs did not reveal a difference with the administration of VPA or CBZ. With respect to the metabolic side-effects of VPA therapy our data indicate that VPA increases glucose stimulated pancreatic insulin secretion, which might be followed by an increase in body weight.

Adult↗

Insulin improves fasting and postprandial lipemia in type 2 diabetes.

BACKGROUND: The purpose of the investigation presented here was to study the effects of insulin therapy in type 2 diabetes mellitus (type 2 DM) not only on glycemic control but also on other components of the metabolic syndrome, including lipid metabolism, blood pressure, and body weight. METHODS: Twelve patients with type 2 DM were studied before and after replacement of sulphonylurea treatment with insulin for 4 months. RESULTS: Insulin therapy resulted in a significant decrease in fasting glucose levels by 26%; glycated hemoglobin decreased by 17% and fructosamine values by 19%. With insulin treatment, fasting plasma triglyceride levels decreased by 28% and total HDL cholesterol and HDL(3) cholesterol increased by 17 and 11%, respectively. Low-density lipoprotein (LDL) cholesterol showed no significant change. The magnitude of postprandial lipemia after ingestion of a standard fatty meal decreased by 38%. Insulin treatment was also accompanied by a 21% increase in lipoprotein lipase (LPL) activity in postheparin plasma and by a 20% increase in cholesteryl ester transfer protein (CETP) activity. Hepatic lipase activity was not changed significantly with insulin. Mean BMI decreased from 28.5+/-4.2 to 28.0+/-3.1 kg/m(2) (P=0.02), which is in keeping with the finding that peripheral insulin levels did not increase and which can be explained by the fact that the insulin regimen was combined with dietary counseling. Accordingly, blood pressure showed no significant change. CONCLUSION: Our study demonstrates that judicious replacement of sulfonylurea treatment with insulin therapy, together with dietary counseling, can result in a simultaneous improvement in the major stigmata of the metabolic syndrome, i.e. a significant improvement in glycemic control and lipid metabolism without unfavorable effects on body weight and blood pressure.

Journal Article↗

Increase in postprandial serum insulin levels in epileptic patients with valproic acid therapy.

A significant weight gain and increase in serum leptin levels in the course of antiepileptic treatment with valproic acid (VPA) has been described in several clinical studies. With respect to the long treatment period in antiepileptic therapy, these side effects might increase insulin resistance and metabolic risk factors. We have studied clinical and laboratory effects of VPA treatment in a cohort of female patients (n = 22) and in patients treated with carbamazepine (CBZ) or lamotrigine monotherapy (n = 21). All study participants underwent an oral glucose tolerance test (OGTT) with 75 g glucose. Body mass index (BMI) in the VPA group was higher (28.1 +/- 3.6 kg/m(2)) than in the control group (23.9 +/- 3.7 kg/m(2)) (P <.039). While plasma glucose, serum leptin, insulin, and C-peptide levels did not differ significantly between the study groups in the fasting state, postprandial (pp) insulin and proinsulin levels were found to be significantly higher in the VPA than in the control group. In the course of the OGTT, serum insulin levels reached their peak values 1 hour postprandially with 68.8 +/- 10.0 microU/mL in the VPA group and 49.8 +/- 11.2 microU/mL in the control group (P <.042). After 2 hours, the corresponding serum insulin levels were 48.5 +/- 25.2 microU/mL and 34.1 +/- 17.2 microU/mL (P <.048) and the proinsulin levels 52.5 +/- 30.2 pmol/L and 29.5 +/- 12.0 pmol/L (P <.017). While BMI values in the non-VPA group showed a significant correlation only with the fasting values of insulin, proinsulin, and C-peptide, the BMI values of the VPA-treated group were also positively related to the 2-hour pp levels of insulin (R =.690; P <.001), proinsulin (R =.667; P <.001) and C-peptide (R =.502; P <.017). VPA is a fatty acid derivative, competes with free fatty acids (FFA) for albumin binding, and acts as a gamma aminobutyric acid (GABA)-ergic agonist, mechanisms, which are known to be involved in pancreatic beta-cell regulation and insulin secretion. Therefore, it might be suspected that VPA therapy is associated with increased glucose stimulated pancreatic secretion and thus a higher body weight in the VPA group.

Adult↗

Decreased high-energy phosphate ratios in the myocardium of men with diabetes mellitus type I.

AIMS/HYPOTHESIS: To investigate whether alterations in high-energy phosphates occur in the myocardium of persons with diabetes mellitus type I. Microvascular abnormalities and dysfunction via thickening of the basement membrane are known to occur in diabetic patients. Myocardial high-energy phosphates have been shown to be reduced by ischemia, and alterations of the cardiac metabolism are the primary consequence of myocardial ischemia. METHODS: The present study involved 34 male patients (mean age 35.5 +/- 10.1) with diabetes mellitus type I and 35 healthy male volunteers (mean age 36 +/- 8.6) as age-matched controls. Phosphorus-31 magnetic resonance spectroscopic imaging of the heart was performed in all subjects using a 1.5-T whole-body magnetic resonance scanner. The ratios of phosphocreatine (PCr) to beta-adenosinetriphosphate (beta-ATP) were calculated. Moreover, echocardiographic evaluation and stress tests were performed in all individuals. RESULTS: The myocardium of patients with diabetes mellitus type I showed significantly decreased ratios of PCr to beta-ATP compared with healthy controls in the left ventricle (1.90 +/- 0.4 vs. 2.15 +/- 0.3, p < 0.05). We found a moderate negative correlation between the ratio of PCr to beta-ATP in the left ventricle and both, the diastolic left ventricular function (E/A; r = -0.41) and the glycohemoglobin A1c (GHbA1c; r = -0.42). CONCLUSION: This study demonstrates for the first time a decreased ratio of PCr to beta-ATP in the myocardium of persons with diabetes mellitus type I without a known history of coronary heart disease.

Adenosine Triphosphate↗

Valproic acid modulates islet cell insulin secretion: a possible mechanism of weight gain in epilepsy patients.

A significant weight gain in the course of treatment of epilepsy with valproic acid (VPA) was described in several clinical studies. We recently demonstrated that postprandial insulin levels are increased in patients with VPA therapy. This possible modulation of pancreatic insulin secretion by VPA could be due to the structure of VPA as a fatty acid derivative and thus to direct stimulation of pancreatic insulin secretion or competition with free fatty acids (FFA) for albumin binding. In order to investigate the effect of VPA on insulin secretion in pancreatic islet cells we performed in vitro experiments with islets from pancreases of multiorgan donors. After preparation, the incubation with valproate caused a time and dose-dependent increase of insulin concentration in the cell supernatant. This could also be demonstrated with the control drug, lorazepam, a benzodiazepine, but not with mirtazepin and phenytoin. It can be speculated that an increase in pancreatic insulin secretion under chronic VPA treatment enhances appetite and energy storage and is related to the observed weight gain.

Cells, Cultured↗