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AIMS To investigate the potential synergistic effects of combined exenatide (EXE) and dapagliflozin (DAPA) versus (PLAC) placebo and DAPA on hepatocellular lipid (HCL) reduction after 24 weeks of treatment. MATERIALS AND METHODS Thirty patients with type 2 diabetes were randomized to weekly EXE and daily DAPA (n = 16) or weekly PLAC and daily DAPA (n = 14). Inclusion criteria were glycated haemoglobin (HbA1c) 48 to 97 mmol/mol (6.5-11%), age 18 to 75 years, body mass index (BMI) ≥25 kg/m2 and metformin ≥1000 mg. The primary endpoint, HCL levels, were measured at baseline and after 24 weeks of treatment using magnetic resonance spectroscopy. Between-group effects were analysed using general linear models, adjusted for baseline outcome variables, age, sex and BMI. Within-group differences were assessed using a paired t-test. RESULTS After 24 weeks, HCLs were reduced in both treatment groups (absolute change from baseline: EXE + DAPA -4.4%, 95% confidence interval [CI] -8.2, -0.7, P

Objective Acetylcarnitine plays an important role in fat metabolism and can be detected in proton magnetic resonance spectra in skeletal muscle. An inverse relationship of acetylcarnitine to intramyocellular lipids and metabolic markers of chronic hyperglycemia has been suggested. This study aimed to compare the acetylcarnitine concentrations and intramyocellular lipids measured noninvasively by proton magnetic resonance spectroscopy (1H MRS) in the tibialis anterior and the soleus of three different groups of volunteers with a broad range of glycemic control. Methods Acetylcarnitine and intramyocellular lipid concentrations were measured in 35 individuals stratified into three groups according to glucose tolerance and/or manifestation of type 2 diabetes mellitus. All MRS measurements were performed on a 3-T MR system. Results The differences in patient phenotype were mirrored by increased intramyocellular lipids in the tibialis anterior and decreased acetylcarnitine concentrations in the soleus muscle of type 2 diabetes patients when compared with normal glucose-tolerant individuals. Results suggest that intramyocellular lipids mirror whole-body glucose tolerance better in the tibialis anterior muscle, whereas acetylcarnitine is a better discriminator in the soleus muscle. Conclusions This muscle-specific behavior of metabolites could represent different fiber compositions in the examined muscles and should be considered when planning future metabolic studies.

Aims To investigate the mechanism of action of 55P0251, a novel multiflorine‐derived substituted quinazolidine that augments insulin release and lowers blood glucose in rodents, but does not act via mechanisms addressed by any antidiabetic agent in clinical use. Materials and Methods Using male mice, we determined the effects of 55P0251 on glucose tolerance, insulin secretion from isolated islets and blood oxygen saturation, including head‐to‐head comparison of 55P0251 to its inverted enantiomer 55P0250, as well as to other anti‐hyperglycaemic multiflorine derivatives discovered in our programme. Results 55P0251 was clearly superior to its inverted enantiomer in the glucose tolerance test (area under the curve: 11.3 mg/kg 55P0251, 1.19 ± 0.04 min*mol/L vs 55P0250, 1.80 ± 0.04 min*mol/L; P

Altres ajuts: Netherlands Organisation for Health Research and Development (ZonMw grant 200310013); Polish Ministry of Science (grants 2203/7, PR/2011/2); Odense University Free Research Fund; Consorcio de Apoyo a la Investigación Biomédica en Red (CAIBER 1527-B-226). Background: Although previous studies evaluated the association of maternal health parameters with neonatal adiposity, little is known regarding the complexity of the relationships among different maternal health parameters throughout pregnancy and its impact on neonatal adiposity. Objectives: To evaluate the direct and indirect associations between maternal insulin resistance during pregnancy, in women with obesity, and neonatal adiposity. In addition, associations between maternal fasting glucose, triglycerides (TG), non-esterified fatty acids (NEFA), and neonatal adiposity were also assessed. Methods: This is a longitudinal, secondary analysis of the DALI study, an international project conducted in nine European countries with pregnant women with obesity. Maternal insulin resistance (HOMA-IR), fasting glucose, TG, and NEFA were measured three times during pregnancy (

OBJECTIVES: To investigate the importance of time in pregnancy and neonatal sex on the association between maternal metabolic parameters and neonatal sum of skinfolds. METHODS: This was a longitudinal, secondary analysis of the vitamin D and lifestyle intervention for gestational diabetes mellitus study, conducted in nine European countries during 2012 to 2015. Pregnant women with a pre-pregnancy body mass index (BMI) of ≥29 kg/m2 were invited to participate. We measured 14 maternal metabolic parameters at three times during pregnancy

Introduction According to the European Agency for Safety and Health at Work (EU-OSHA), hospitals represent a work environment with high job strain. Prolonged perceived occupational stress may result in symptoms of burnout, such as emotional exhaustion (EE), depersonalisation (DP) and reduced personal accomplishment (PA). Understanding which factors may reduce vulnerability for burnout is an important requirement for well-targeted occupational stress prevention in mental hospital staff. Objective To identify the influence of gender, age, working field, family structure, education, voluntarily occupational training during holidays and length of stay on job on occupational stress perception. Methods In a cross-sectional design, 491 employees (311 female, 180 male) of an Austrian mental health centre participated in the study. The extent of perceived occupational stress was assessed by the Maslach Burnout Inventory (MBI) with the scales for emotional exhaustion, depersonalisation and personal accomplishment. Participants were divided according to their working field in those working with/without patients. Findings Prevalence of emotional exhaustion was higher in women working with patients compared to men working with patients (25% vs. 18%, p = 0.003). Age above 45 years was significantly associated with decreased vulnerability for burnout in men (EE p = 0.040, DP p = 0.010, PA p = 0.007), but not in women. A lower level of education had a significant impact on depersonalisation in both sexes (p = 0.001 for men, p = 0.048 for women). Length of stay on job showed a significant influence on emotional exhaustion. No significant relationship was found between family structure and vulnerability for burnout. Conclusion Gender had a differential effect on perceived occupational stress indicating a need for gender-tailored preventive strategies. Age, working field, education, voluntarily occupational training during holidays and length of stay on job affect vulnerability for burnout in mental hospital staff.

BACKGROUND Obesity is known to induce a deterioration of insulin sensitivity (SI ), one of the insulin-dependent components of glucose tolerance. However, few studies investigated whether obesity affects also the insulin-independent component, that is glucose effectiveness (SG ). This cross-sectional study aimed to analyse SG and its components in different body mass index (BMI) categories. MATERIALS AND METHODS Three groups of subjects spanning different BMI (kg m-2 ) categories underwent a 3-h frequently sampled intravenous glucose tolerance test: Lean (LE; 18.5 ≤ BMI

Aim There is firm evidence of a relation between type 2 diabetes (T2DM) and increased risks of cancer at various sites, but it is still unclear how different antihyperglycaemic therapies modify site-specific cancer risks. The aim of this study was to provide a complete characterization of all possible associations between individual T2DM therapies, statin use and site-specific cancers in the Austrian population. Methods Medical claims data of 1 847 051 patients with hospital stays during 2006–2007 were used to estimate age- and sex-dependent co-occurrences of site-specific cancer diagnoses and treatment with specific glucose-lowering drugs and statins. Results Patients treated with insulin or insulin secretagogues showed up to ninefold increased risks for cancers of the colon [males only (m)], liver (m), pancreas, lung (m) and brain (m), as well as a strongly decreased risk for prostate cancer (m). In patients taking statins, the risks were generally decreased, with a greater risk reduction in patients not receiving antihyperglycaemic therapies. The strongest effects were observed for use of insulin and pancreatic cancer [m: OR 4.5, 95% CI: 3.1–6.6; females (f): OR 4.2, 95% CI: 2.5–7.1], sulfonylureas (m: OR 2.8, 95% CI: 1.7–4.6; f: OR 3.0, 95% CI: 2.1–4.2) or glitazones and skin cancer (f: OR 0.54, 95% CI: 0.36–0.80), as well as metformin and cancer of the prostate (m: OR 0.82, 95% CI: 0.75–0.91) and corpus uteri (f: OR 1.7, 95% CI: 1.4–2.0) and non-Hodgkin's lymphoma (f: OR 0.76, 95% CI: 0.64–0.91). Conclusions The use of statins offsets insulin-related cancer risks in patients with diabetes independently of sex and age. Overall, our data support the hyperglycaemia–cancer hypothesis. A reduction in endogenous or exogenous hyperinsulinaemia may be beneficial for cancer prevention. Therefore, insulin-sparing and insulin-sensitizing drugs should be the preferred treatment choices.

Rising rates of diabetes in pregnancy have led to an escalation in research in this area. As in any area of clinical research, definitions of outcomes vary from study to study, making it difficult to compare research findings and draw conclusions. Our aim was to compile and create a repository of definitions, which could then be used universally. A systematic review of the literature was performed on published and ongoing randomized controlled trials in the area of diabetes in pregnancy between 01 Jan 2000 and 01 Jun 2012. Other sources included the World Health Organization and Academic Society Statements. The advice of experts was sought when appropriate definitions were lacking. Among the published randomized controlled trials on diabetes and pregnancy, 171 abstracts were retrieved, 64 full texts were reviewed and 53 were included. Among the ongoing randomized controlled trials published in ClinicalTrials.gov, 90 protocols were retrieved and 25 were finally included. The definitions from these were assembled and the final maternal definitions and foetal definitions were agreed upon by consensus. It is our hope that the definitions we have provided (i) will be widely used in the reporting of future studies in the area of diabetes in pregnancy, that they will (ii) facilitate future systematic reviews and formal meta analyses and (iii) ultimately improve outcomes for mothers and babies.

Aims To determine the impact of gender on glycaemic control and hypoglycaemia in insulin-naive patients with type 2 diabetes (T2DM). Methods Data were pooled from six randomized clinical trials of insulin glargine or NPH insulin in insulin-naive, inadequately controlled patients. Female [n = 1251; mean glycated haemoglobin (HbA1c) level 8.99%, age 56.91 years, diabetes duration 9.84 years] and male patients (n = 1349; mean HbA1c 8.9%, age 57.47 years, diabetes duration 10.13 years) were started on and treated with insulin glargine or NPH insulin for 24–36 weeks. HbA1c and fasting blood glucose levels, percent achieving HbA1c target of

Objective To assess the association between diabetes mellitus (DM) and metformin use with prognosis and outcomes of non-muscle-invasive bladder cancer (NMIBC) PATIENTS AND METHODS: We retrospectively evaluated 1117 patients with NMIBC treated at four institutions between 1996 and 2007. Cox regression models were used to analyse the association of DM and metformin use with disease recurrence, disease progression, cancer-specific mortality and any-cause mortality. Results Of the 1117 patients, 125 (11.1%) had DM and 43 (3.8%) used metformin. Within a median (interquartile range) follow-up of 64 (22-106) months, 469 (42.0%) patients experienced disease recurrence, 103 (9.2%) experienced disease progression, 50 (4.5%) died from bladder cancer and 249 (22.3%) died from other causes. In multivariable Cox regression analyses, patients with DM who did not take metformin had a greater risk of disease recurrence (hazard ratio [HR]: 1.45, 95% confidence interval [CI] 1.09-1.94, P = 0.01) and progression (HR: 2.38, 95% CI 1.40-4.06, P = 0.001) but not any-cause mortality than patients without DM. DM with metformin use was independently associated with a lower risk of disease recurrence (HR: 0.50, 95% CI 0.27-0.94, P = 0.03). Conclusion Patients with DM and NMIBC who do not take metformin seem to be at an increased risk of disease recurrence and progression; metformin use seems to exert a protective effect with regard to disease recurrence. The mechanisms behind the impact of DM on patients with NMIBC and the potential protective effect of metformin need further elucidation.

Objective The development of overt diabetes in women with prior gestational diabetes mellitus (priorGDM) has been linked to several risk factors including age, obesity and insulin therapy during pregnancy; the role of recurrent GDM as a further risk factor remains unclear. As studies examining detailed metabolic consequences of recurrent GDM are missing and the role of recurrent GDM on cardiovascular risk is unknown, our aim was to investigate the impact of recurrent GDM (within 5 years after an index pregnancy) on metabolic and cardiovascular parameters. Methods Oral and intravenous glucose tolerance tests as well as assessment of cardiovascular risk factors were performed at baseline (6 months after index pregnancy) and 5 years thereafter in 21 prior GDM with recurrent GDM (recGDM), 41 prior GDM with no additional pregnancy (nonrecGDM) and 10 healthy controls [CON]. Results Despite weight gain in recGDM (2·3 ± 5·1 vs. −1·3 ± 6·7 kg, P

The impact of sex and age on glucose metabolism in the development of overweight/obesity is a matter of debate. We hypothesized that insulin sensitivity (IS) and β-cell function (BF) in a normal white population will differ between males and females and aimed to evaluate the possible effects of BMI and age on metabolic parameters of both sexes. This study is a cross-sectional analysis of the general community. IS was measured with quantitative insulin sensitivity check index (QUICKI) and oral glucose insulin sensitivity (OGIS) and BF with the insulinogenic index during 75-g 2-h oral glucose-tolerance tests (OGTTs). We studied 611 females and 361 males with normal glycemia according to both fasting and 2-h glucose (85 ± 0.3 mg/dl (means ± SE) in females and 89 ± 0.4 in males (P < 0.0001), and 93 ± 1 in females and 89 ± 1 in males (P = 0.005), respectively). Females were younger (37 ± 1 years) than males (40 ± 1, P < 0.0001), but no difference was found in mean BMI (BMI = 25.8 ± 0.2 kg/m(2) in both). Student's two-sample t-test was used for simple comparison between and within genders, multiple linear regressions to account for covariates. During the OGTT, females had lower glucose (area under the curve (AUC) 133 ± 1 mg/ml·2 h vs. 148 ± 2; P < 0.00001), while insulinemia was comparable (AUC 5.3 ± 0.1 mU/ml·2 h vs. 5.7 ± 0.2, P = 0.15). IS remained higher in females (473 ± 3 ml/min/m(2) vs. 454 ± 3, P < 0.0001) also after having accounted for age and BMI (P = 0.015). No difference was observed in fasting insulin or BF. However, BF increased by 46% with BMI and when accounting for age and BMI, BF of females was significantly higher (P < 0.0001). Because IS and BF are higher in females than in males, sex should be considered in metabolic studies and overweight/obese populations.

Summary Objective To evaluate the relationship of plasma fetuin-A levels with markers of bone turnover in male and female type 2 diabetic subjects. Background Fetuin-A, which is a serum protein produced by the liver and promotes bone mineralization, is an independent risk factor for type 2 diabetes, whilst type 2 diabetes is associated with an increased incidence of osteoporosis or fractures. It is not known how fetuin-A levels relate to parameters of bone metabolism in type 2 diabetes. Design and patients Eighty patients with type 2 diabetes [40 men and 40 women matched for age, body mass index (BMI) and time since diagnosis of diabetes] were studied. Fetuin-A together with metabolic parameters and levels of serum carboxy-terminal telopeptide of type 1 collagen (C-telopeptide), osteocalcin, procollagen type 1 amino-terminal propeptide (P1NP), bone alkaline phosphatase (ALP) and sex hormones was determined in all participants. Results Fetuin-A levels did not differ significantly between male and female diabetic subjects. In a model adjusted for age, BMI, fatty liver index (FLI), time since diagnosis of diabetes, HbA1c, antidiabetic and lipid-lowering drug therapies, smoking, total serum protein, creatinine, gamma glutamyl-transferase, parathyroid hormone, C-reactive protein, glomerular filtration rate, and presence of micro-, cardio-, and peripheral vascular diabetic complications, fetuin-A showed a significant positive association with levels of bone ALP (r = 0·71, P = 0·006) in men. In women, fetuin-A was significantly negatively associated with C-telopeptide (r = −0·60, P = 0·03) levels. Conclusions Results suggest an independent association of fetuin-A levels with markers of bone turnover in male and female patients with type 2 diabetes. More studies are needed to determine whether fetuin-A could serve as a new marker for fracture risk or osteoporosis in type 2 diabetes and to explore its potential sexually dimorphic effects.

Diabet. Med. 29, 351–358 (2012) Abstract Aims Women with former gestational diabetes are at increased risk of Type 2 diabetes, which likely relates to hyperlipidaemia and ectopic lipid storage, mainly in the liver. Here, we examined the response of non-esterified fatty acid dynamics to oral glucose loading (oral glucose tolerance test). Methods We studied women with former gestational diabetes with normal glucose tolerance (n = 60) or impaired glucose metabolism (n = 12) and compared them with healthy women after normal pregnancy (control subjects, n = 15). During a 3-h oral glucose tolerance test, glucose, insulin and non-esterified fatty acid were frequently measured to compute the area under the non-esterified fatty acid curve and parameters of β-cell function and insulin sensitivity. Through mathematical modelling, we assessed insulin sensitivity of lipolysis inhibition and the fractional non-esterified fatty acid turnover rate. We also measured some serum liver enzymes. Results Women with former gestational diabetes were slightly older and had greater body mass than control subjects. Subjects with impaired glucose metabolism had lower oral glucose insulin sensitivity, but higher fasting insulin and area under the non-esterified fatty acid curve, which inversely related to oral glucose insulin sensitivity and independently determined mean glycaemia. Model-derived non-esterified fatty acid parameters were lower in subjects with impaired glucose metabolism than in control subjects, particularly sensitivity of non-esterified fatty acid inhibition to insulin (2.50 ± 0.52 vs. 1.06 ± 0.20·10−2 ml/μU). Also, subjects with impaired glucose metabolism had higher liver transaminases. However, all non-esterified fatty acid parameters showed only modest inverse correlation with liver transaminases. Conclusions Despite greater insulinaemia, circulating non-esterified fatty acids are higher in women with former gestational diabetes than in control subjects, which likely results from reduced sensitivity of lipolysis inhibition to insulin. This parameter may serve as indicator of an early metabolic derangement in this population at risk for diabetes.

Background Clinicians and health professionals are increasingly challenged to understand and consider the different health needs of women and men. The increase of gender awareness and the expanding science of gender medicine will affect more and more clinical practice. This review addresses gender-specific aspects in metabolic disorders and related complications, which represent an increasing burden of this century and a great challenge to public health. Design There is increasing evidence of gender-related differences in risk factors, clinical manifestation and sequelae of obesity and diabetes and increasing knowledge that prevention, detection and therapy of illness affect men and women differently. Results Some gender-specific aspects, especially regarding cardiovascular disease, have been studied in more detail, but for many complications sex-related analyses of the results of both clinical trials and basic science are still missing or disregarded. Impaired glucose and lipid metabolism as well as dysregulation of energy balance and body fat distribution have a great impact on overall health via neuroendocrine changes and inflammatory pathways and deteriorate the course of many diseases with particular harm for women. Metabolic diseases dramatically affect life of men and women from infancy up to old age and are a major challenge for women during pregnancy. Great impact is attached to the intrauterine period and the lifelong implications of fetal programming. Conclusions Initiation of prospective studies on the impact of gender as primary outcome and investigation of gender-related pathophysiological mechanisms of chronic diseases will help to improve patient care and to implement evidence-based gender-specific prevention programs and clinical recommendations in future.

Objective. Women with previous gestational diabetes mellitus (GDM) have a high risk for development of type 2 diabetes mellitus. The endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) could be related to disorders of the glucose metabolism. To evaluate if ADMA predicts deterioration of glucose tolerance in women with previous GDM and to assess concentration changes we analysed ADMA in women with previous GDM after delivery and after a median follow-up of 2.75 years (interquartile range: 1.47–4.60). Design. Prospective cohort study. Subjects and methods. ADMA, symmetric dimethylarginine (SDMA) and l-arginine were determined in 77 women with previous GDM who underwent a 75-g oral glucose tolerance test 4 months after delivery and at follow-up. Results. Deterioration in glucose tolerance was observed in 36% of the women with ADMA above and 11% of those with ADMA below the median (0.56 μmol L−1; P = 0.008, log-rank test). ADMA correlated significantly with mean arterial blood pressure and nonsignificantly with body mass index (P = 0.050) but not with insulin resistance, fasting glucose, lipids or glomerular filtration rate. The fully adjusted hazard ratio for a decline of glucose tolerance during follow-up was 3.94 (95% CI: 1.16–13.37; P = 0.028) for subjects with ADMA above the median. SDMA and l-arginine were not associated with changes in the glucose tolerance status. ADMA and l-arginine decreased significantly during follow-up. Conclusions. High serum ADMA after delivery is associated with deterioration in glucose tolerance in women with previous GDM and declines in the following years.

Background Cardiac autonomic neuropathy is a common dysfunction in manifest diabetes mellitus and is associated with duration of diabetes and/or an inadequate glycaemic control. Heart rate variability (HRV) reflects autonomic heart function. The aim of the present study was to investigate whether in women with prior gestational diabetes (GD; pre-type 2 diabetes) alterations of cardiac autonomic function can be observed after delivery in relation to insulin sensitivity and glycaemic control. Materials and methods Forty-eight healthy women with prior GD were consecutively admitted to the study. HRV was analysed by both time, as well as frequency, domain methods using 24-h Holter monitoring. In addition, 20 women with normal glucose tolerance during and after pregnancy were investigated as control subjects. All women underwent a frequently sampled intravenous glucose tolerance test (FSIGT) for measurement of insulin sensitivity. Results Time domain analysis (standard deviation of normal RR intervals; SDNN) showed a reduced HRV in 25 out of the 48 (52%) women with prior GD. Frequency domain analysis revealed that in these 25 subjects both low and high frequency components of power spectral density (reflecting mainly sympathetic respectively parasympathetic activity) were reduced, indicating that sympathetic as well as parasympathetic functional impairment may be assumed. However, a relative predominance of the sympathetic over parasympathetic cardiac function was observed. The impairment of cardiac autonomic function (reduced SDNN) was correlated with HbA1c values and the 2-h blood glucose concentration (oral glucose tolerance test) but not with insulin sensitivity. Conclusion The present results demonstrate that in 52% of the women examined who had prior GD, an impairment of cardiac sympathetic as well as parasympathetic function was present, which related to glycaemic control, but not to insulin sensitivity. This infers that functional autonomic changes could be an early prognostic indicator in pre-type 2 diabetes.

Rising rates of diabetes in pregnancy have led to an escalation in research in this area. As in any area of clinical research, definitions of outcomes vary from study to study, making it difficult to compare research findings and draw conclusions. Our aim was to compile and create a repository of definitions, which could then be used universally. A systematic review of the literature was performed on published and ongoing randomized controlled trials in the area of diabetes in pregnancy between 01 Jan 2000 and 01 Jun 2012. Other sources included the World Health Organization and Academic Society Statements. The advice of experts was sought when appropriate definitions were lacking. Among the published randomized controlled trials on diabetes and pregnancy, 171 abstracts were retrieved, 64 full texts were reviewed and 53 were included. Among the ongoing randomized controlled trials published in ClinicalTrials.gov, 90 protocols were retrieved and 25 were finally included. The definitions from these were assembled and the final maternal definitions and foetal definitions were agreed upon by consensus. It is our hope that the definitions we have provided (i) will be widely used in the reporting of future studies in the area of diabetes in pregnancy, that they will (ii) facilitate future systematic reviews and formal meta analyses and (iii) ultimately improve outcomes for mothers and babies. Copyright (c) 2015 John Wiley & Sons, Ltd.

Aim: This study was designed to assess the usefulness of a model-based index of insulin sensitivity during an oral glucose tolerance test (OGTT) in the identification of possible changes in this metabolic parameter produced by pharmacological agents known to be potent insulin sensitizers, that is metformin (M) and thiazolidinedione (T). The association of these agents with several other factors related to glucose metabolism was also investigated, as well as the relation of insulin sensitivity and secretion with markers of endothelial function such as different adhesion molecules (cAMs), that is vascular cell adhesion molecule-1, intercellular adhesion molecule-1 and E-Selectin. Methods: Twenty type 2 diabetic patients treated with diet only underwent a 3-h OGTT for measurement of plasma glucose, insulin, proinsulin, C-peptide and cAMs before and after administration of randomly given M (n = 9; 1700 mg/day) or T (n = 11; 600 mg/day). After 16 weeks of treatment, a second OGTT was performed. Insulin sensitivity was calculated with homeostasis model assessment and with oral glucose insulin sensitivity (OGIS), which quantifies dynamic glucose clearance per unit change of insulin. Insulin secretion was assessed by modelling technique. Differences in these parameters before and after treatment, as well as possible relationships with cAMs, were assessed. Results: Basal and stimulated plasma glucose decreased after therapy in both the groups by approximately 20%. Basal insulin resistance also decreased. Insulin sensitivity in dynamic conditions (OGIS: ml/min/m2) increased with M (289.3 ± 18.8 vs. 234.7 ± 18.1, p

Background Women with a history of gestational diabetes (p-GDM) are at increased risk of developing type 2 diabetes mellitus (DM2) later in life, and therefore at increased risk for future cardiovascular disease. Materials and methods Three months after delivery we investigated the plasma levels of plasminogen activator inhibitor type 1 (PAI-1), tissue plasminogen activator (t-PA), fibrinogen and von Willebrand factor (vWF) in 74 women with p-GDM and 20 healthy females with normal glucose tolerance during and after pregnancy, as well as the relation of fibrinolytic parameters to insulin resistance and glycaemic control. All women underwent an oral (OGTT) as well as an intravenous glucose tolerance test (FSIGT). Mathematical model analysis disclosed that 50% (n = 37 each) of the p-GDM subjects had normal (NIS) or impaired (IIS) insulin sensitivity. Parameters of interest were determined using commercially available test systems. Results Women with p-GDM and IIS had significantly increased body fat mass (BFM) (P ≤ 0·001) compared with women with p-GDM and NIS and controls, whereas the waist to hip ratio (WHR) was similar in both p-GDM groups but was higher compared with the controls (P ≤ 0·001). Mean PAI-1 and t-PA as well as fasting and stimulated plasma concentrations of proinsulin, C-peptide and insulin were elevated, whereas the disposition index was lower in women with p-GDM and IIS compared with women with p-GDM and NIS and the controls (P

Background Growth hormone deficiency is associated with increa~ed morbidity and mortality from cardiovascular diseases, which might be related to changes in glucose and lipid metabolism. Design To assess the infiuence oflong-term growth hormone replacement therapy (GHRT) on glucose metabolism we examined eight growth hormone-deficient (GHD) adults (seven female/one male; age, 46 ± 3 years; body mass index, 31 ± 2 kg m -2) over aperiod of 18 months in comparison to an adequate control group consisting of eight obese subjects matched for age, sex, and body mass index. We performed frequently sampled intravenous glucose tolerance tests (FSIGT) with minimal model analysis before the study, and after 12 and 18 months. Results FoHowing GHRT, insulin-like growth factor-1 (IGF-1) increased significantly from a basal level of75·9 ± 18·9 to 200·8 ± 31·0 JLgL-1 after 12 months oftherapy and remained stable, thereafter. GHRT did not affect fasting blood glucose, basal insulin, cholesterol, blood pressure and body weight. However, at 12months, HbA1c (6·0 ± 0·1 vs. 5·6 ± 0·1 % at b~sal, P< 0·05) and triglyceride (2·3 ± 0·4 vs. 1·4 ± 0·3 mmol L-1) significantly increased but returned to pretreatment values at 18 months. Insulin sensitivity was higher in GHD (8·2 ± 3·1) compared to controls (3·6 ± 0·53 x 10- 4 min-l/(JLU mL-1), P= 0·06) and decreased significantly after 18 months of GHRT to 5·1 ± 2·6, P< 0·05. Basal insulin secretion was similar to that in the control group and increased significantly after 12 and 18 months, total insulin secretion only after 12 months. SG (glucose effectiveness)was lower in GHD patients (0·0095 ± 0·001 min- 1 ) compared to controls (0·020 ± 0·003 min-l, P

Background Plasma leptin is considered to play a role in maintenance of energy balance and body weight by neuroendocrine mechanisms. Thyroid hormones are permissive for adrenergic activation, which in turn has been shown to decrease leptin expression. This study was therefore designed to test the hypothesis that hyperthyroidism results in lower leptin concentrations, whereas hypothyroidism leads to higher plasma leptin concentrations. In addition, the effects of normalization of thyroid function on plasma leptin were investigated. Materials and methods Fasting plasma leptin concentrations and body fat mass (total body electrical conductivity) were measured in patients with overt hypothyroidism and hyperthyroidism before and after successful treatment. Plasma leptin, glucose, insulin and free fatty acid concentrations were monitored during an oral glucose tolerance test (OGTT 75 g). Results Fasting plasma leptin concentrations were similar in lean patients, independently of their thyroid function (hyperthyroid 12.5 ± 2 ng mL−1, hypothyroid 10.2 ± 2 ng mL−1, euthyroid 12.7 ± 3 ng mL−1). In obese hypothyroid patients, plasma leptin was threefold higher (P