Showing papers in "Experimental and Clinical Endocrinology & Diabetes in 2008"
TL;DR: The development of efficient screening strategies for type 2 diabetes risk as well as the development of core intervention strategies for the primary prevention of type 1 diabetes should significantly enhance the ability of health care professionals to respond swiftly to the drastic increase of T2D and its burden to the society.
Abstract: Background The prevalence of type 2 diabetes (T2D) has dramatically increased in Europe, and the age-at-diagnosis has become younger. Action is needed now to develop targeted prevention management program for T2D. The DE-PLAN ("Diabetes in Europe - Prevention using Lifestyle, Physical Activity and Nutritional intervention") project, led by the University of Helsinki is currently addressing this major public health concern in Europe. Methods The DE-PLAN project aims at developing and testing models of efficient identification and intervention of individuals at high risk of type 2 diabetes in the community. It conducts a lifestyle modification intervention in people at high risk for T2D. Furthermore, it tests the feasibility and cost-effectiveness of the translation of the current research evidence about preventive intervention program into clinical settings within existing health care systems in 17 European countries. Results This 3-year project spanning has commenced mid-2005. By now, 25 institutions from 17 countries are involved. Conclusion The development of efficient screening strategies for type 2 diabetes risk as well as the development of core intervention strategies for the primary prevention of type 2 diabetes should significantly enhance the ability of health care professionals to respond swiftly to the drastic increase of T2D and its burden to the society.
170 citations
TL;DR: The data suggest that the increased body weight in carriers of the risk allele of FTO SNP rs8050136 is a consequence of increased food intake, but not of impaired energy expenditure.
Abstract: Polymorphisms in the FTO (fat mass- and obesity-associated) gene are associated with obesity. The mechanisms how genetic variation in this gene influences body weight are unknown. Body weight is determined by energy intake/storage and energy expenditure. In this study, we investigated whether genetic variation in FTO influences energy expenditure or food intake in carefully phenotyped subjects. In 380 German subjects, insulin sensitivity was measured by a hyperinsulinemic euglycemic clamp. Lean body mass and body fat were quantified using the bioimpedance method. Indirect calorimetry was used to estimate the metabolic rate. Food intake was assessed using food diaries (mean 11+/-1 d) in 151 subjects participating in a lifestyle intervention program to prevent diabetes. All subjects were genotyped for the FTO single nucleotide polymorphism (SNP) rs8050136. The risk allele of SNP rs8050136 was associated with higher body fat-related parameters (all p< or =0.04, additive inheritance model). Energy expenditure was not affected by the SNP. However, the risk allele of rs8050136 was significantly associated with higher energy intake (p=0.01, dominant inheritance model) during dietary restriction. Our data suggest that the increased body weight in carriers of the risk allele of FTO SNP rs8050136 is a consequence of increased food intake, but not of impaired energy expenditure.
166 citations
TL;DR: Benfotiamine may extend the treatment option for patients with diabetic polyneuropathy based on causal influence on impaired glucose metabolism and increased with treatment duration.
Abstract: Aim Efficacy and safety of benfotiamine in treatment of diabetic polyneuropathy. Methods Double blind, placebo-controlled, phase-III-study. 181 patients were screened. 165 patients with symmetrical, distal diabetic polyneuropathy were randomised to one of three treatment groups entering the wash-out phase and 133/124 patients were analysed in the ITT/PP analysis: Benfotiamine 600 mg per day (n=47/43), benfotiamine 300 mg per day (n=45/42) or placebo (n=41/39). Results After 6 weeks of treatment, the primary outcome parameter NSS (Neuropathy Symptom Score) differed significantly between the treatment groups (p=0.033) in the PP (per protocol) population. In the ITT (intention to treat) population, the improvement of NSS was slightly above significance (p=0.055). The TSS (Total Symptom Score) showed no significant differences after 6 weeks of treatment. The improvement was more pronounced at the higher benfotiamine dose and increased with treatment duration. In the TSS, best results were obtained for the symptom "pain". Treatment was well tolerated in all groups. Conclusion Benfotiamine may extend the treatment option for patients with diabetic polyneuropathy based on causal influence on impaired glucose metabolism. Further studies should confirm the positive experiences.
147 citations
TL;DR: Plasma apelin is reduced in newly diagnosed and untreated patients with type 2 diabetes mellitus having no confounders and Regulation of circulating apelin and adiponectin seems to be in the same manner in patients with T2DM.
Abstract: Objective: To investigate blood apelin concentrations in patients with newly diagnosed and untreated type 2 diabetes mellitus (T2DM) who had no additional disorder and to investigate the association of apelin with adiponectin, body mass indexes (BMI) and insulin sensitivity. Methods: Forty patients with T2DM and 40 healthy controls were enrolled. Apelin levels were measured along with BMI, lipids, glucose, insulin and adiponectin levels, and HOMA-IR indexes. Age, sex and BMI were similar in the two groups. Results: Plasma apelin and adiponectin levels were significantly lower in the diabetic group compared to controls (p<0.001, for both). Insulin levels and HOMA indexes were significantly higher in patients with T2DM (p<0.001 and p=0.001, respectively). Apelin levels were negatively correlated with age (r= -0.315, p=0.006), fasting blood glucose (r=-0.556, p<0.001) and HOMA indexes (r=-0.411, p=0.001), and positively correlated with plasma adiponectin levels (r=0.593, p<0.001). Plasma adiponectin was negatively correlated to plasma insulin (r= -0.379, p=0.001), fasting glucose (r= -0.604, p<0.001), HOMA-IR (r=-0.559, p<0.001) and BMI (=-0.229, p=0.04). Conclusions: Plasma apelin is reduced in newly diagnosed and untreated patients with T2DM having no confounders. Regulation of circulating apelin and adiponectin seems to be in the same manner in patients with T2DM. Dysregulation of apelin might be involved in the mechanism of establishment of overt diabetes mellitus as well as associated atherosclerotic complications.
128 citations
TL;DR: Both obesity and Type 2 diabetes are independently associated with an increased risk of developing cancer and an increased mortality.
Abstract: Both obesity and Type 2 diabetes are independently associated with an increased risk of developing cancer and an increased mortality. The etiology is yet to be determined but insulin resistance and hyperinsulinemia maybe important factors. Hyperglycemia, hyperlipidemia and inflammatory cytokines in addition to the insulin-like growth factors are also possible factors involved in the process.
117 citations
TL;DR: A review of the current state of transcriptome profiling techniques and the results of a series of transciptome studies comparing bovine endometrium samples from pregnant vs. non-pregnant animals can be found in this article.
Abstract: The endometrium undergoes marked functional changes during estrous cycle and pregnancy. As the adjacent environment of the conceptus, it represents the maternal interface for embryo-maternal communication, which is essential to maintain pregnancy. Transcriptome studies provide the unique opportunity to assess molecular profiles changing in response to endocrine or metabolic stimuli or to embryonic pregnancy recognition signals. Here we review the current state of transcriptome profiling techniques and the results of a series of transciptome studies comparing bovine endometrium samples during the estrous cycle or endometrium samples from pregnant vs. non-pregnant animals. These studies revealed specific mRNA profiles which are characteristic for the functional status of the endometrium. Transcriptome studies of endometrial samples recovered during the pre-attachment period identified many interferon-stimulated genes, genes that are possibly involved in embryo-maternal immune modulation (C1S, C1R, C4, SERPING1, UTMP, CD81, IFITM1, BST2), as well as genes affecting cell adhesion (AGRN, CD81, LGALS3BP, LGALS9, GPLD1, MFGE8, and TGM2) and remodeling of the endometrium (CLDN4, MEP1B, LGMN, MMP19, TIMP2, TGM2, MET, and EPSTI1). The results of these transcriptome studies were compared to those of similar microarray analyses in human, mouse and Rhesus monkey to identify similarities in endometrial biology between mammalian species and species-specific differences. Future studies will cover dynamic transcriptome changes between different stages of early pregnancy, the relationship between metabolic problems in dairy cows and the functionality of reproductive tissues as well as endometrium transcriptome profiles in recipients of somatic cell nuclear transfer embryos.
114 citations
TL;DR: In this article, the authors analyzed cortisol in hair donated by mothers with a neonate child (n-Mothers; N=103), mothers with toddlers 3-9 months of age, and control women (n=20) and concluded that cortisol measured in human hair can be a valid reflection of increased cortisol production for up to six months.
Abstract: Hair has long been used in toxicology, forensic science, doping control and other fields as a biological specimen for the detection of environmental agents, drugs, or toxins. Most recent evidence suggests that also hormones are incorporated and trapped inside the growing hair. This has led to the hypothesis that cortisol measurement of distinct hair segments could provide a retrospective calendar of cortisol production for the individual. In this first proof-of-concept study in humans, we analyzed cortisol in hair donated by mothers with a neonate child (n-Mothers; N=103), mothers with toddlers 3-9 months of age (t-Mothers; N=19), and control women (N=20). We cut hair strands from each women into at least three 3-cm segments, which, based on an average hair growth rate of 1cm per month, would represent hair grown over the past three, six, and nine months, respectively. Since in the third trimester of pregnancy there is a well-documented increased production of cortisol, we expected to see elevated levels of cortisol in the most proximal hair segment of women who had just given birth to a child (n-Mothers) compared with the control women. Likewise, we expected to see elevated levels in the second, third, or fourth segment of mothers of 3-month olds, 6-months olds, and 9-months olds, respectively. These hair segments, cut at 4-12 cm from the scalp, would represent hair grown throughout the third trimester of pregnancy. Results showed that there was a strong monotonic decline in cortisol concentration from the segment closest to the scalp to the most distal hair segment (p 0.2). When hair from mothers with 6-9 months old toddlers was analyzed, the hair segment representing the third trimester period contained the same amount of cortisol as the hair grown more recently in mothers with 3-4 months old toddlers only. Age of the women, hair curvature, hair color, and frequency of hair washes per week were unrelated to cortisol levels. We conclude that cortisol measured in human hair can be a valid reflection of increased cortisol production for a period of up to six months. Due to a rapid decline of cortisol levels in human adult hair, a retrospective calendar of cortisol exposure may be limited to the past six months.
108 citations
TL;DR: Results show that MSCs transplantation improved cardiac function in the rat DCM model, possibly through angiogenesis and attenuation of cardiac remodeling.
Abstract: Independent of the severity of coronary artery disease, diabetic patients have an increased risk of developing heart failure. Diabetic cardiomyopathy (DCM) is characterized by microvascular pathologies and interstitial fibrosis. Mesenchymal stem cells (MSCs) are pluripotent and are able to differentiate into cardiomyocytes and vascular endothelial cells. Studies have demonstrated MSCs transplantation can prevent apoptosis of ischemic heart via upregulation of Akt and eNOS and inhibit myocardial fibrosis of dilated cardiomyopathy by decreasing the expression of matrix metalloproteinase (MMP) in rat models. In order to find out whether transplantation of MSCs is a promising treatment in DCM, we used streptozotocin (STZ) -induced diabetic rats as the model. Exogenous MSCs were injected into the femoral vein 8 weeks after STZ injection. Using independent experimental approaches, we showed that MSCs presented in the myocardium 4 weeks after transplantation and some of them were positive for the cardiac markers Troponin T and myosin heavy chain. MSCs transplantation significantly increased myocardial arteriolar density and decreased the collagen volume in diabetic myocardium resulting in improved cardiac function. Furthermore, MSCs transplantation increased MMP-2 activity and decreased transcriptional level of MMP-9. These results show that MSCs transplantation improved cardiac function in the rat DCM model, possibly through angiogenesis and attenuation of cardiac remodeling.
102 citations
TL;DR: In CNCP patients receiving chronic opioid therapy there is a much higher prevalence of hypogonadism in men then in women, and this needs to be considered clinical practice.
Abstract: The effect of chronic oral opioids on hypothalamus-pituitary-gonadal axis in women, and on bone mineral density (BMD) in men and women is not known The objective of this cross-sectional study was to determine the effect of long-term oral opioids on gonadal status and BMD in male and female patients with chronic non-cancer pain (CNCP) We included 26 community-dwelling CNCP patients, 12 men and 14 premenopausal women, treated with oral opioids for at least one year We obtained Visual Analogue Scale for pain score, BMD and plasma LH and FSH in all patients; menstrual history and estradiol in women; free androgen index and total and free testosterone in men Men were older then women (p<005) and had used opioids for a longer period (72+/-38 and 41+/-18 years, respectively; p<005), but there was no difference in opioid dose or pain score between sexes The prevalence of hypogonadism was high in men (75%), while only 21% of the women reported oligo- or amenorrhea indicating hypogonadism (P<001, between sexes) Osteopenia was found in 50% of men and 21% of women (p=NS) We conclude that in CNCP patients receiving chronic opioid therapy there is a much higher prevalence of hypogonadism in men then in women This needs to be considered clinical practice
99 citations
TL;DR: The hypothesis that metformin can abrogate AGE-induced deleterious effects in osteoblastic cells in culture is evaluated and AGEs-treatment of osteoblast-like cells enhanced RAGE protein expression, and this up-regulation was prevented in the presence of met formin.
Abstract: Advanced glycation endproducts (AGEs) are implicated in the complications of diabetes and ageing, affecting several tissues, including bone. Metformin, an insulin-sensitizer drug, reduces the risk of life-threatening macrovascular complications. We have evaluated the hypothesis that metformin can abrogate AGE-induced deleterious effects in osteoblastic cells in culture. In two osteoblast-like cell lines (UMR106 and MC3T3E1), AGE-modified albumin induced cell death, caspase-3 activity, altered intracellular oxidative stress and inhibited alkaline phosphatase activity. Metformin-treatment of osteoblastic cells prevented these AGE-induced alterations. We also assessed the expression of AGE receptors as a possible mechanism by which metformin could modulate the action of AGEs. AGEs-treatment of osteoblast-like cells enhanced RAGE protein expression, and this up-regulation was prevented in the presence of metformin. Although the precise mechanisms involved in metformin signaling are still elusive, our data implicate the AGE-RAGE interaction in the modulation of growth and differentiation of osteoblastic cells.
89 citations
TL;DR: The endocrine regulation of equine parturition involves progestagens, oestrogens, PGs and oxytocin as in other species but there are differences in placental hormone synthesis and in the timing and magnitude of key prepartum endocrine changes between species.
Abstract: Delivery of viable young requires co-ordination of fetal maturation with the onset of labour at term In turn, this depends on a cascade of fetal and maternal endocrine events The sequence of these events is broadly similar in most mammals but there are differences in placental hormone synthesis and in the timing and magnitude of key prepartum endocrine changes between species In most farm animals, maternal progesterone (P4) levels decline and oestrogen levels increase in the last 5 - 10 days before delivery in response to activation of the fetal hypothalamicpituitary-adrenal (HPA) axis and increased fetal cortisol concentrations This cortisol surge is also responsible for fetal maturation and increasing uteroplacental prostaglandin (PG) synthesis In the mare, there is little, if any, P4 in the maternal plasma during late gestation and both progestagens and oestrogens are produced by a feto-placental unit which uses precursors supplied by the fetus to synthesise a range of C21 and C18 steroids, many of which are unique to the horse Regulation of uterine quiescence and activation is, therefore, complex in the mare near term Indeed, total progestagen concentrations rise and total oestrogen levels fall in the mare during the last 20 - 30 days of gestation and only show the changes typical of impending parturition in other species in the last 24 - 48 h before delivery Fetal cortisol concentrations also rise late in gestation in the horse compared to other species In common with other species, the prepartum endocrine cascade appears to begin in the fetal horse with activation of the fetal HPA axis but, initially, the primary product of the fetal equine adrenal appears to be pregnenolone (P5) and not cortisol This leads to increased progestagen production by the uteroplacental tissues, which maintains uterine quiescence in the face of increasing uterine stretch caused by the rapidly growing fetus Very close to term in association with increasing fetal ACTH levels, the fetal equine adrenals appear to switch to producing cortisol This late cortisol surge induces a period of rapid fetal maturation and may also contribute to increased uteroplacental oestradiol-17 beta and PG production The fall in P5 availability may reduce uteroplacental progestagen production and lift the block on myometrial contractility Finally, increased PG secretion activates myometrial contractions, which stimulate oxytocin release via a neuroendocrine reflex The endocrine regulation of equine parturition, therefore, involves progestagens, oestrogens, PGs and oxytocin as in other species However, further studies are required to establish the causes and consequences of the rise and fall in maternal progestagens and the extent to which initiation of equine labour depends on the fetal HPA axis
TL;DR: The prevalence of vitamin D deficiency in pregnant women and their newborns in Isfahan, a sunny city in Iran is determined to be 5.7% and 4.5% according to local definition.
Abstract: BACKGROUND AND AIMS Vitamin D deficiency is one of the major health problems and unexpectedly has a high prevalence in sunny countries (e.g. Middle East). In this study we determined the prevalence of vitamin D deficiency in pregnant women and their newborns in Isfahan, a sunny city in Iran. METHODS In a cross-sectional study, 88 newborns born in Beheshty hospital, affiliated to Isfahan University of Medical Sciences (August-September, 2005) and their mothers were studied. Their data were collected by questionnaires and blood sampling was done to measure serum alkaline phosphatase (ALP), calcium, phosphorus, 25 (OH) vitamin D and parathormone (PTH). Vitamin D deficiency defined as levels of 25 (OH) D < 20 and < 12.5 ng/ml for mothers and newborns, respectively and local cut-offs defined as levels in which mean serum PTH started to increase. RESULTS The prevalence of vitamin D deficiency according to 25 (OH) D < 20 ng/ml in mothers and < 12.5 ng/ml in newborns was 5.7% and 4.5%, respectively. According to local cut-offs (35 ng/ml for mothers and 26 ng/ml for newborns) 26.1% of mothers and 53.4% of newborns were vitamin D deficient. CONCLUSION According to local definition, vitamin D deficiency is a health problem in pregnant women and their newborns in this sunny city.
TL;DR: A significant association of vaspin SNP rs2236242 with T2DM is demonstrated in the KORA F3 study with the AA genotype bearing an increased risk (adjusted OR 2.35 [1.59; 3.46] versus AT/TT).
Abstract: Vaspin has recently been identified as novel adipokine with high expression in adipose tissue of obese and type 2 diabetic subjects and with potentially insulin-sensitising properties. However, the impact of vaspin gene variants on the risk of type 2 diabetes mellitus (T2DM) has not been determined yet. Therefore, the aim of our study was to investigate the association of vaspin single nucleotide polymorphisms (SNPs) with T2DM and obesity. We analysed the association between 25 vaspin SNPs and T2DM in initially healthy 35-84 year-old individuals of the population-based, cross-sectional German KORA F3 study and assessed the association with measures of obesity. Genotyping was carried out with matrix-assisted laser desorption/ionisation-time of flight mass spectrometry of allele-dependent primer extension products and associations with T2DM and obesity were analysed by logistic regression analysis. Our results demonstrate a significant association of vaspin SNP rs2236242 with T2DM in the KORA F3 study with the AA genotype bearing an increased risk (adjusted OR 2.35 [1.59; 3.46] versus AT/TT). This association appears to be independent of obesity. Our finding corroborates previous studies that suggested a link between the novel adipokine vaspin and glucose metabolism.
TL;DR: The effects of Astragalus polysaccharides on the prevention of type 1 DM in NOD mice were demonstrated by correcting the imbalance between the Th1/Th2 cytokines.
Abstract: Background Type 1 diabetes mellitus (DM) is a chronic autoimmune disease that is related to the disequilibrium state of Th1 and Th2 subgroups of helper T lymphocyte (Th) and their cytokines. Astragalus polysaccharides (APS) are bioactive components extracted from one of the traditional Chinese herbs, used to enhance the function of human immune system. Objective To investigate the effects of APS on preventing type 1 DM and Th1/Th2-subtype cytokines, we compared the results of administration of APS and normal saline (NS) on non-obese diabetic (NOD) mice. Subjects and methods APS or NS was administered to 4-week-old mice at a dose of 2.0 g/kg per day for 10 weeks. At 40 weeks, blood glucose, serum C-peptide (C-P) and GAD antibody were measured; pancreas was examined histologically; the intra-islet lymphocyte infiltration and T lymphocyte subsets in the spleen were analysed; the gene expression of IL-1 beta, IL-2, IL-6, IL-12, TNF-alpha, INF-gamma, IL-4, IL-5, IL-10, TGF-beta, Bcl-2, SOD, Fas and iNOS were measured by RT-PCR. Results The results showed that APS-administered NOD mice had a lower incidence rate of type 1 DM, lower serum C-P level, better histologic findings of pancreatic islets, and a lower D4+/CD8+ ratio of T lymphocytes from the spleen and the infiltrated islets. RT-PCR analysis showed gene expression levels are lower in IL-1 beta, IL-2, IL-6, IL-12, TNF-alpha, INF-gamma, Fas, iNOS, and higher in IL-4, IL-5, IL-10, TGF-beta, Bcl-2, SOD in the pancreatic tissue from APS-administered NOD mice as compared to the NS group. Conclusions These results demonstrated the effects of Astragalus polysaccharides on the prevention of type 1 DM in NOD mice by correcting the imbalance between the Th1/Th2 cytokines.
TL;DR: Despite some evidence from recent studies for putative roles of placental steroids in cattle their exact functions in the bovine species remain still undefined.
Abstract: The bovine placenta produces large amounts of steroids, mainly estrone (E1) and progesterone (P4). Specific features of bovine placental steroidogenesis are 1) the expression of all enzymes needed for the production of estrogens from cholesterol in the trophoblast 2) an only marginal and temporal contribution to peripheral maternal P4 levels restricted to a period between approx. days 150 - 240 of gestation 3) the predominance of sulfoconjugated over free E1 and 4) a complementary setting of steroidogenic enzymes in the two morphologically discriminable trophoblast cell types, the uninucleated trophoblast cells (UTC) and the trophoblast giant cells (TGC). In cattle so far no definite information is available on the specific biological roles of placental estrogens and P4. However, the detection of estrogen receptors and progesterone receptors in the placentomes suggests a role primarily as local regulators of caruncular growth, differentiation and functions. Inconsistent with a function as a caruncular growth factor is the strong evidence that in cattle placental estrogens enter the maternal compartment almost completely as estrone sulfate (E1S), which is not active at classical nuclear receptors. On the other hand, E1S may be converted locally to free active estrogens via the action of steroid sulfatase (StS), which has been detected in specific parts of the bovine caruncular epithelium. Alternatively or in addition, StS expression in the caruncular epithelium may serve the utilization of sulfated neutral steroid precursors (e.g. pregnenolone sulfate or cholesterol sulfate) supplied with maternal blood, thus providing free substrates for further metabolization in the adjacent trophoblast. The down-regulation of P450scc and P450c17 and the up-regulation of 3beta-HSD and aromatase during the differentiation of TGC from UTC in parallel with the up-regulation of ER beta and estrogen sulfotransferase in maturing TGC suggests a function of placental estrogens primarily as autoor intracrine regulators during this process and assigns to conjugated placental estrogens a role as inactivated by-products of TGC differentiation intended for excretion. Collectively, despite some evidence from recent studies for putative roles of placental steroids in cattle their exact functions in the bovine species remain still undefined.
TL;DR: A novel mechanism of how the cyclic hypoxemia in OSA predisposes OSA patients to cardiovascular disease through the dysregulation of secretion of APN by adipocytes is suggested.
Abstract: Obstructive sleep apnea (OSA), characterized by cyclic intermittent hypoxia (IH) during sleep, is an independent risk factor for cardiovascular disease. Adiponectin (APN), an adipocytokine secreted exclusively by adipocytes, possesses antiatherogenic properties. Low levels of APN, particularly the high-molecular-weight (HMW) form, are associated with an increased risk of cardiovascular disease. Here, we hypothesized that IH would result in the dysregulation of APN expression and secretion. 3T3-L1 adipocytes were exposed to IH at 12 cycles/h for 6 h/d to simulate the IH condition similar to that encountered in OSA. Control adipocytes were exposed to 21% O(2) under identical conditions. After 48 h of incubation, IH caused a decrease in the secretion of total and HMW APN in spite of a significant upregulation of APN mRNA expression by adipocytes. This study suggested a novel mechanism of how the cyclic hypoxemia in OSA predisposes OSA patients to cardiovascular disease through the dysregulation of secretion of APN by adipocytes. Further studies are needed to determine the exact molecular mechanism how IH reduces the release of APN by adipocytes.
TL;DR: Although no data is available relating the direct effect of herpes infection on thyroid epithelial cells, a better understanding of how an aberrant immune response against the thyroid gland is initiated and propagated through herpes virus infection is required.
Abstract: Aim To demonstrate any differences in the detection of herpes simplex virus type 1 and 2, cytomegalovirus, human herpes virus type 6 and 7 DNA from thyroid tissue blocks of patients with autoimmune thyroid disease and multi-nodular goiter and to propose few mechanisms, which could explain the possible role of herpesvirus infection in the development of thyroid autoimmune responses. Material-methods Thyroid tissue specimens were obtained postoperatively from 4 patients with multinodular goiter and 18 patients with autoimmune thyroid disease (Graves' disease and Hashimoto thyroiditis). Herpes virus DNA was detected using polymerase chain reaction based assays. Results No statistically significant differences were observed between autoimmune thyroid disease and multinodular goiter tissue specimens concerning herpes simplex virus type 1, 2 DNA isolation (44.4% vs 0%, P=0.094), human herpes virus type 6 DNA isolation (11.1% vs 0%, P=0.48), human herpes virus type 7 DNA isolation (33.3% vs 25%, P=0.75). No CMV DNA was isolated from any tissue specimen. At least one kind of herpes virus DNA was detected in 13 out of 18 (72.22%) AITD tissue specimens and in 1 out of 4 (25%) MNG tissue specimens (P=0.01). Conclusions Although no data are available relating the direct effect of herpes infection on thyroid epithelial cells, a better understanding of how an aberrant immune response against the thyroid gland is initiated and propagated through herpes virus infection is required. Elucidation of the underlying mechanisms may allow the development of new etiologically based therapeutic modalities.
TL;DR: Investigating whether the levels of proinflammatory factors in PCOS patients are related to sequence variations of the PPAR gamma gene revealed evidence for a direct association of PPAR Gamma with altered IL-7, IL-1beta,IL-6 and TNFalpha levels in PCos patients.
Abstract: The Polycystic ovary syndrome (PCOS) is the most frequent endocrine disorder in premenopausal women and is associated with features of the insulin resistance syndrome, altered glucose homeostasis, and central obesity. Inflammation appears to be a link between obesity and insulin resistance, because adipose tissue is one major source of proinflammatory cytokines. Since peroxisome proliferator-activated receptor (PPAR)gamma affects adipocyte differentiation as well as insulin sensitivity, we investigated whether the levels of proinflammatory factors in PCOS patients are related to sequence variations of the PPAR gamma gene. Proinflammatory cytokine levels, i.e. IL-1 beta, IL-6, IL-7, IL-8, IL-17 and TNFalpha, were evaluated in PCOS patients (n=21) in comparison to obese controls (n=120). Next to this the complete coding sequence of the PPAR gamma gene was investigated by resequencing all probands. We show that the levels of IL-8 and IL-17 were unchanged, IL-1 beta, IL-6 and TNFalpha were elevated and the level of IL-7 was decreased in PCOS patients compared to obese controls. Sequence analyses of the PPAR gamma gene indicated that neither the common polymorphisms P12A or H478 H, nor novel polymorphisms (E79Q, V32G, -39 T>C, c.480 +33 t > g,) or unique sequence variations (S22S, A23A, T41A, S226C, K272 T, I484I, c.819 +24 a>c) detected in this investigation revealed evidence for a direct association of PPAR gamma with altered IL-7, IL-1beta, IL-6 and TNFalpha levels in PCOS patients. So, alterations in inflammatory serum markers appear to be a feature of PCOS per se, and are independent of PPAR gamma variants.
TL;DR: Sensitive CRP was found to be statical significantly higher in polycystic ovary syndrome groups whose Homeostasis Model Assessment-Insulin Resistance were > or =1.75 when compared to the control group and no significantly correlation was determined between malondialdehyde, nitric oxide and disulfide levels and CRP elevation.
Abstract: Objective: Polycystic ovary syndrome is a syndrome of ovarian dysfunction. Oxidative stress, inflammation and endothelial cell activation are thought to play concomitant roles in the pathogenesis of the above diseases particularly in the development of atherosclerotic lesions. Research Design and Methods: We studied 58 polycystic ovary syndrome patients and age-matched 25 healthy controls consisting of women that have regular, ovulatory cycles and normal androgen levels. Homeostasis Model Assessment-Insulin Resistance for this study was taken as 1.75 that is the upper level of confidence interval of %95 of the mean of the healthy group. PCOS patients were divided into two groups as for below the cut-off level (<1,75) and above the cutoff level (≥ 1.75). hs-CRP, fibrinogen, malondialdehyde, nitric oxide and disulfide level results were compared both in PCOS and control groups. Results: In this study, sensitive CRP was found to be statical significantly higher in polycystic ovary syndrome groups whose Homeostasis Model Assessment-Insulin Resistance were ≥ 1.75 and <1.75 when compared to the control group. But, no significantly correlation was determined between malondialdehyde, nitric oxide and disulfide levels and CRP elevation. Conclusions: In our study, because those participants were young and non- obese patients with PCOS, malondialdehyde, nitric oxide and disulfide levels and Carotid Artery Intima-Media Thickness measurements as a pre-indicator of cardiovascular disease were not found to be different from those of the controls.
TL;DR: Investigation of the role of adiponectin serum levels and gene polymorphisms in the development of diabetic retinopathy in patients with diabetes mellitus type 2 demonstrated the proof of principle that adip onectin is detectable in the fluid of the human vitreous body.
Abstract: INTRODUCTION Even diabetic patients with excellent glycemic control can develop diabetic complications very early. Possibly, not only the degree of glycemic control, but other factors as well are responsible for the development of diabetic microangiopathy. Since adiponectin represents an adipocyte-specific secretory protein modulating endothelial cell functions, it was the aim of the present study to investigate the role of adiponectin serum levels as well as adiponectin gene polymorphisms in the development of diabetic retinopathy. METHODS A population based cohort of caucasian patients (n=523) with type 2 diabetes mellitus was recruited from an epidemiological field survey. Serum adiponectin levels were determined by ELISA. Genotypes of the Tyr111His and the Gly15Gly polymorphism were determined by PCR-based RFLP analysis. Diabetic retinopathy was graded by fundus photography. RESULTS The data demonstrate, that a) the Tyr111His (T-->C) polymorphism influences adiponectin serum levels, b) adiponectin serum levels do correlate with the prevalence of diabetic retinopathy, and c) patients heterozygous for the +45 T-->G (Gly15Gly) polymorphism show a lower prevalence of diabetic retinopathy. Furthermore, we could generate the proof of principle that adiponectin is detectable in the fluid of the human vitreous body. SUMMARY Adiponectin gene polymorphisms influence adiponectin serum levels and elevated adiponectin serum levels are associated with diabetic retinopathy in patients with diabetes mellitus type 2. Therefore, endothelial cell modulating adiponectin should be further investigated as a candidate gene in the development and progression of retinopathy associated with type 2 diabetes mellitus.
TL;DR: T1D treatment needs to be improved overall and close attention should be paid to T2 diabetics with a 5-9-year diabetes history, with the aim of preventing any loss of metabolic control.
Abstract: Introduction: The quality of glycaemic control of patients with T1D and T2D can be assessed with HbA 1c levels. We aimed to assess the qual- ity of glycaemic control and the prevalence of inadequately controlled diabetes in German pri- mary care, and to determine simple patient and treatment related factors associated with poor control. Material and Methods: Using a nationwide probability sample of 3 188 general practices (response rate 50.6 % ), a total of 55,518 patients were assessed in DETECT, a cross-sectional and prospective multistage epidemiological study. Diabetes diagnoses were based on physician assessment. HbA 1c values were taken from the patient charts. Results: The quality of metabolic control was unsatisfactory on the whole in the 277 peo- ple with T1D (e.g. mean HbA 1c = 7.4 % ± 1.4 % ). The 8 188 people with T2D had a mean HbA 1c of 6.89 % ± 1.2 % . 38.8 % of individuals had an HbA 1c ≥ 7.0 % . The situation was less favourable in subjects with a longer history of diabetes - in many cases in those with diabetes for 5 - 9 years, but generally in those with a plus-10-year his- tory of diabetes - and also in younger men with a shorter disease history. Patients with a short T2D history, especially older subjects had more favourable values. With regard to age, a higher percentage of patients had an HbA 1c ≥ 7.0 % (42.0 % and 40.6 % ) in the 45 - 54 and 55 - 64 year olds. With respect to the correlation between HbA 1c and treatment modality, we identifi ed the best metabolic control in T2D patients with- out drug therapy for diabetes, and the worst in patients on combination regimens (OAD / insulin). The average duration of diabetes in the various treatment groups differs substantially. The aver- age duration was highest (12.1 y) in the insulin group. Oral treatment was the predominant treatment modality in all HbA 1c categories. Conclusion: T1D treatment needs to be improved overall. The situation as regards T2D is less clear-cut. When people with T2D start requiring more intensive and complex treatment in response to disease progression, the treatment efforts of patients and physicians evidently fail to keep up with the actual pace of metabolic deteri- oration. Early and strict alignment with approxi- mately normal HbA 1c targets is essential. Close attention should be paid to T2 diabetics with a 5 - 9-year diabetes history, with the aim of pre- venting any loss of metabolic control. Likewise, patients aged 45 - 64 y and younger men require more attention.
TL;DR: Foot temperature is significantly higher in type 2 diabetic patients with neuropathy as compared to those without neuropathy, and a significant positive correlation is observed between foot temperature and clinical severity of neuropathy.
Abstract: UNLABELLED The aim of this study was to evaluate foot temperature in type 2 diabetic patients with vs. without peripheral neuropathy. The study included 30 patients (group A: 16 men, mean age 63.23+/-7.02 years) with peripheral neuropathy and 30 patients (group B: 17 men, mean age 62.37+/-6.73 years) without peripheral neuropathy. Neuropathy was diagnosed by the Diabetic Neuropathy Index (DNI). Foot temperature was measured with a handheld infrared thermometer (KM 814, Kane-May, UK) on the mid-dorsal aspect of the foot (dorsal temperature) and on the plantar aspect of the foot at the level of the first metatarsal head (plantar temperature). Dorsal temperature was significantly higher in group A than in group B (right foot 32.89+/-1.02 degrees C vs. 31.2+/-1.07 degrees C, p<0.001). The same significant difference was observed for the plantar temperature (32.2+/-0.94 degrees C vs. 30.7+/-1.07 degrees C, p<0.001). In both groups, a significant positive correlation was observed between dorsal and plantar temperature (group A: r (s)=0.913, p<0.001; group B: r (s)=0.956, p<0.001). Finally, in group A, DNI score showed a significant positive correlation with dorsal temperature (r (s)=0.856, p<0.001), as well as plantar temperature (r (s)=0.859, p<0.001). CONCLUSIONS Foot temperature is significantly higher in type 2 diabetic patients with neuropathy as compared to those without neuropathy. In patients with neuropathy, a significant positive correlation is observed between foot temperature and clinical severity of neuropathy.
TL;DR: It is concluded that VEGF-A is required in pancreatic islets for normal glucose-stimulated insulin secretion and physiological insulin content and is a key factor for pancreas islet function.
Abstract: Mice, deficient for vascular endothelial growth factor VEGF-A in pancreatic islets, have reduced insulin gene expression levels and an impaired glucose tolerance. Here, we investigated whether VEGF-A was required for physiological glucose-stimulated insulin secretion and insulin content. We performed in situ pancreas perfusions and islet perifusions on mice lacking VEGF-A in the pancreatic epithelium in order to study their ability to secrete insulin in response to glucose. We identified insulin secretion defects in the pancreata of VEGF-A deficient mice, including a delayed and blunted response to glucose. Islet perifusion experiments revealed a missing first phase and weaker second phase of insulin secretion, in two of three VEGF-A deficient mice. On average, insulin content in VEGF-A deficient islets was significantly reduced when compared with control islets. We conclude that VEGF-A is required in pancreatic islets for normal glucose-stimulated insulin secretion and physiological insulin content. Thus, VEGF-A is a key factor for pancreatic islet function.
TL;DR: Altered muscle fiber distribution and enzyme activities seem to be due to impaired long-term glycemic control, most likely due to both a higher number of fast glycolytic fibers and a shift towards increased glyCOlytic metabolism in all fiber types.
Abstract: We investigate muscle fiber composition, fiber-specific glycolytic and oxidative enzyme capacity and nitric oxide synthase (NOS) expression in skeletal muscle of patients with type 1 diabetes (T1D) compared to individuals with normal glucose tolerance (NGT). Vastus lateralis muscle was obtained by percutaneous biopsy from 7 T1D patients and 10 healthy controls with similar characteristics. Using cytophotometry, muscle fiber composition and fiber type-specific glycolytic and oxidative enzyme activities were measured in slow oxidative (SO), fast oxidative glycolytic (FOG) and fast glycolytic (FG) fibers. In addition, NOS 1-3 protein expression was mea-sured. The glycolytic fiber fraction was 1.4 fold higher, whereas FOG and SO fiber fractions were significantly reduced by 13.5% and 6.2% in skeletal muscle from T1D patients. Glycolytic enzyme activities and fiber-specific ratio of glycolytic relative to oxidative enzyme activity were significantly higher in all fiber types of T1D patients and correlated with HbA 1c . Expression of NOS1-3 isoforms was reduced in skeletal muscle of T1D subjects. Increased glycolytic enzyme activity in muscle of T1D patients is most likely due to both a higher number of fast glycolytic fibers and a shift towards increased glycolytic metabolism in all fiber types. Alterations in muscle fiber distribution and enzyme activities seem to be due to impaired long-term glycemic control.
TL;DR: Two sisters, who displayed nephrolithiasis or nephrocalcinosis upon presentation, are described, who had undergone left nephro-ureterectomy at age 17 because of ureteral stricture secondary to renal calculi and with oral phosphate supplements, hypophosphatemia and hypercalciuria improved.
Abstract: Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is caused by mutations in SLC34A3, the gene encoding the renal sodium-phosphate co-transporter NaPi-IIc. Despite increased urinary calcium excretion, HHRH is typically not associated with kidney stones prior to treatment. However, here we describe two sisters, who displayed nephrolithiasis or nephrocalcinosis upon presentation. The index patient, II-4, presented with short stature, bone pain, and knee X-rays suggestive of mild rickets at age 8.5 years. Laboratory evaluation showed hypophosphatemia, elevated 1,25(OH) (2) vitamin D levels, and hypercalciuria, later also developing vitamin D deficiency. Her sister, II-6, had a low normal serum phosphorous level, biochemically vitamin D deficiency and no evidence for osteomalacia, but had undergone left nephro-ureterectomy at age 17 because of ureteral stricture secondary to renal calculi. Nucleotide sequence analysis of DNA from II-4 and II-6 revealed a homozygous missense mutation c.586G>A (p.G196R) in SLC34A3/NaPi-IIc. Ultrasonographic examinations prior to treatment showed grade I nephrocalcinosis for II-4, while II-6 had grade I-II nephrocalcinosis in her remaining kidney. Four siblings and the mother were heterozygous carriers of the mutation, but showed no biochemical abnormalities. With oral phosphate supplements, hypophosphatemia and hypercalciuria improved in both homozygous individuals. Renal calcifications that are presumably due to increased urinary calcium excretion can be the presenting finding in homozygous carriers of G196R in SLC34A3/NaPi-IIc, and some or all laboratory features of HHRH may be masked by vitamin D deficiency.
TL;DR: AIP mutations are rare in sporadic pituitary adenomas in the German population and occur independently from a hormone secretion of the adenoma.
Abstract: OBJECTIVE: Recent data suggest that mutations in the aryl hydrocarbon receptor interacting protein gene (AIP) are associated with pituitary adenomas. AIP is considered to be a tumour suppressor gene. METHODS: 110 Caucasian patients living in Germany with pituitary adenoma (55 hormone secreting, 55 non-functioning) were examined for AIP mutations. RESULTS: Three patients (2.7%) harboured an AIP germline mutation. A heterozygous mutation, R16H (c.47G>A), was found in two patients and a heterozygous G>C change in the 3’UTR, 60 bp downstream of the termination codon, in one patient. All three patients suffered from non-functioning adenoma. Additionally, a silent polymorphism, D172D (c.516C>T), was found in 3 patients with non-functioning adenoma, in 2 patients with prolactinoma and in one patient with acromegaly. CONCLUSIONS: AIP mutations are rare in sporadic pituitary adenomas in the German population and occur independently from a hormone secretion of the adenoma.
TL;DR: Investigating changes in the DC compartment in the peripheral blood in type 2 diabetes found Hyperglycemic metabolism does affect the pool of peripheral DCs and leads to a reduction of both, mDC1 and pDC.
Abstract: OBJECTIVE: It is a common clinical experience that type 2 diabetic patients are susceptible to opportunistic infections. The underlying reasons for this immune deficiency are not yet understood. Dendritic cells (DC) play a key role in initiating innate and adapted immune responses. DESIGN: In order to investigate changes in the DC compartment in the peripheral blood in type 2 diabetes, we analyzed blood from patients under poor and good metabolic control and compared them to healthy controls. PATIENTS: 5 mls of blood were collected from 15 healthy controls, 15 diabetic patients with an HbA1c >7.0 and 15 patients with an HbA1c <9.5%. Age range was 44-80 years. Patients were age-matched with the control group. MEASUREMENT: Blood DC were enumerated by flow cytometry after staining with antibodies against the blood dendritic cells antigens 1-3 (BDCA 1-3). This allows quantification of the DC subtypes: myeloid dendritic cells type 1 (mDC1, mDC2) and plasmacytoid dendritic cells (pDC). RESULTS: The relative and absolute frequency for both mDC1 and pDC was clearly diminished in patients with poor metabolic control as compared to healthy controls. In patients with good metabolic control the reduction of DC was less pronounced but still significant, particularly for mDC1. CONCLUSION: Hyperglycemic metabolism does affect the pool of peripheral DCs and leads to a reduction of both, mDC1 and pDC. Even patients considered to be under good metabolic control appear to have a reduced peripheral pool of DC.
TL;DR: In this article, the diagnostic potential of copeptin, the C-terminal part of provasopressin, as a new marker in the differential diagnosis of hyponatremia was evaluated.
Abstract: Background: Treatment of patients with hyponatremia varies widely; thus, convenient diagnostic parameters are needed to guide the correct treatment strategy. This study was designed to evaluate the diagnostic potential of copeptin, the C-terminal part of provasopressin, as a new marker in the differential diagnosis of hyponatremia. Methods: In this prospective observational study, 106 consecutive hyponatremic patients were classified based on their history, clinical evaluation, and laboratory tests. In patients and 32 healthy control subjects, plasma copeptin concentration and standard biochemical parameters were tested for their utility of diagnosing the syndrome of inappropriate antidiuresis (SIAD). Results: Four patients (4%) were diagnosed as primary polydipsia, nine (8%) as diuretic-induced hyponatremia, 42 (40%) as SIAD, 29 (27%) as hypovolemic hyponatremia, and 22 patients (21%) as hypervolemic hyponatremia. In controls, a close correlation between plasma copeptin and serum sodium (r2 = 0.62, P < 0...
TL;DR: The major findings of this study were that the plasma OPG concentrations were higher in type 2 diabetic patients than O PG concentrations in healthy control subjects and they were positively correlated with diabetic neuropathy.
Abstract: Background and aims To investigate the association of plasma osteoprotegerin (OPG) levels with diabetic neuropathy. Methods Forty-two diabetic patients (21 female and 21 male) and twenty-four non-diabetic healthy control subjects (12 female and 12 male) were included in the study. All consecutive diabetic patients who came for routine follow-up at our outpatient clinic were invited to participate in this clinical study. We studied EMG and neuropathy symptom score in all study subjects. Fasting plasma glucose, HbA1 C, hs-CRP, OPG levels and lipid profile were measured for each subject. Results Serum fasting glucose, HbA1c, HOMA-IR, total cholesterol, triglyserid, LDL-Cholesterol, HDL-Cholesterol, lipoprotein (a), apolipoprotein-b, hs-CRP, OPG levels, and neuropathy symptom score were statistically higher in diabetic patients than in healthy control subjects. Plasma OPG levels was statistically higher in diabetic patients than it was in nondiabetic control subjects. However, plasma OPG levels were not significantly different between diabetic patients without neuropathy and healthy control subjects. On the other hand, OPG levels were statistically higher in diabetic patients with neuropathy than in patients without neuropathy. In addition to that serum fasting glucose, HbA1c, hs-CRP, diabetes duration, neuropathy symptom score were statistically higher in diabetic patients with neuropathy than they were in patients without neuropathy. In total group of subjects, plasma OPG levels were correlated significantly with age, diabetes duration, HbA1c, total cholesterol, HDL-cholesterol, lipoprotein (a), apolipoprotein b, hs-CRP. In diabetic patients, plasma OPG correlated significantly with age, diabetes duration, neuropathy symptom score, HbA1c, lipoprotein (a), apolipoprotein b levels. Conclusions The major findings of this study were that the plasma OPG concentrations were higher in type 2 diabetic patients than OPG concentrations in healthy control subjects and they were positively correlated with diabetic neuropathy. This finding supports the growing concept that OPG acts as an important regulator in the development of vascular dysfunction in diabetes.
TL;DR: Treatment with altrenogest did not prevent parturition and its effectiveness to prevent abortion or preterm foalings in mares with disturbed pregnancies should be doubted.
Abstract: In this study, effects of altrenogest treatment (0.088 mg/kg daily) given to mares during late gestation until parturition on the time and the process of foaling, neonatal adaptation and postnatal development were analysed. The number of animals was 6 in the treatment group and 7 in the control group. Gestational length tended to be shorter in mares given altrenogest. Birth weight of the foals and weight of the placenta did not differ between groups. The second stage of parturition was prolonged in the altrenogest-treated mares (p<0.05). Foals born to altrenogest-treated mares had a significantly lower respiratory rate than control foals during the first 30 minutes of life (p<0.05). At no time differences in heart rate and body temperature were found between groups. In foals of altrenogest treated mares, venous plasma pH was significantly higher than in control foals at 15 and 30 minutes after birth (p<0.05). Base excess in foals of altrenogest treated mares was significantly higher than in control foals at 45 minutes and up to 12 hours after birth (p<0.05). There were significantly more problems in the perinatal period (3/6) in foals born after altrenogest treatment to their dams than in control foals (0/7; p<0.05). In conclusion, treatment with altrenogest did not prevent parturition and its effectiveness to prevent abortion or preterm foalings in mares with disturbed pregnancies should be doubted. In addition, altrenogest treatment of mares affected adaptation of the foals to the extrauterine environment.