Lipocalin-type prostaglandin D synthase levels increase in patients with narcolepsy and idiopathic hypersomnia

SLEEP ◽  
2020 ◽  
Author(s):  
Peipei Wang ◽  
Qinghua Li ◽  
Xiaosong Dong ◽  
Haiyan An ◽  
Jing Li ◽  
...  
Keyword(s):  
Cerebral Spinal Fluid ◽  
Sleep Latency ◽  
Healthy Controls ◽  
Lower Serum ◽  
Central Origin ◽  
Prostaglandin D Synthase ◽  
Idiopathic Hypersomnia ◽  
Hypocretin 1

Abstract Study Objectives Excessive daytime sleepiness (EDS) is a frequent cause for consultation and a defining symptom of narcolepsy and idiopathic hypersomnia (IH). The associated mechanisms remain unclear. Lipocalin-type prostaglandin D synthase (LPGDS) is a plausible sleep-inducing candidate. This study is to compare cerebral spinal fluid (CSF) and serum LPGDS levels in patients group with hypersomnia of central origin, including those with narcolepsy type 1 (NT1) and type 2 (NT2) and IH, to those in healthy controls (Con). Methods Serum LPGDS, CSF LPGDS, and CSF hypocretin-1(Hcrt-1) levels were measured by ELISA in 122 narcolepsy patients (106 NT1 and 16 NT2), 27 IH, and 51Con. Results LPGDS levels in CSF (p = 0.02) and serum (p < 0.001) were 22%–25% lower in control subjects than in patients with EDS complaints, including NT1, NT2, and IH. In contrast to significant differences in CSF Hcrt-1 levels, CSF L-PGDS levels and serum L-PGDS were comparable among NT1, NT2, and IH (p > 0.05), except for slightly lower serum LPGDS in IH than in NT1 (p = 0.01). Serum L-PGDS correlated modestly and negatively to sleep latency on MSLT (r = −0.227, p = 0.007) in hypersomnia subjects. Conclusions As a somnogen-producing enzyme, CSF/serum LPGDS may serve as a new biomarker for EDS of central origin and imply a common pathogenetic association, but would complement rather than replaces orexin markers.

scholarly journals Cerebrospinal fluid monoamine levels in central hypersomnolence disorders

SLEEP ◽  
2021 ◽  
Author(s):  
Lucie Barateau ◽  
Isabelle Jaussent ◽  
Julien Roeser ◽  
Claudio Ciardiello ◽  
Thomas S Kilduff ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Daytime Sleepiness ◽  
Direct Consequence ◽  
Trace Amines ◽  
Idiopathic Hypersomnia ◽  
National Reference Center ◽  
Drug Free ◽  
Sleep Propensity

Abstract Study objectives Whether the cause of daytime sleepiness in narcolepsy type 1 (NT1) is a direct consequence of the loss of orexin neurons or whether low orexin reduces the efficacy of the monoaminergic systems to promote wakefulness is unclear. The neurobiology underlying sleepiness in other central hypersomnolence disorders, narcolepsy type 2 (NT2) and idiopathic hypersomnia (IH), is currently unknown. Methods Eleven biogenic amines including the monoaminergic neurotransmitters and their metabolites and five trace amines were measured in the cerebrospinal fluid (CSF) of 94 drug-free subjects evaluated at the French National Reference Center for Narcolepsy: 39 NT1(orexin-deficient) patients, 31 patients with objective sleepiness non-orexin deficient (NT2 and IH), and 24 patients without objective sleepiness. Results Three trace amines were undetectable in the sample: Tryptamine, Octopamine, and 3-iodothyronamine. No significant differences were found among the three groups for quantified monoamines and their metabolites in crude and adjusted models; however, CSF 5-HIAA levels tended to increase in NT1 compared to other patients after adjustment. Most of biomarkers were not associated with ORX-A levels, clinical or neurophysiological parameters, but a few biomarkers (e.g., MHPG and norepinephrine) correlated with daytime sleepiness and high REM sleep propensity. Conclusion We found no striking differences among CSF monoamines, their metabolites and trace amine levels, and few associations between them and key clinical or neurophysiological parameters in NT1,NT2/IH and patients without objective sleepiness. Although mostly negative, these findings are a significant contribution to our understanding of the neurobiology of hypersomnolence in these disorders that remain mysterious and deserve further exploration.

scholarly journals A cross sectional study to compare cardiac structure and diastolic function in adolescents and young adults with youth-onset type 1 and type 2 diabetes: The SEARCH for Diabetes in Youth Study

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Amy S. Shah ◽  
Scott Isom ◽  
Dana Dabelea ◽  
Ralph D’Agostino ◽  
Lawrence M. Dolan ◽  
...  
Keyword(s):  
Risk Factors ◽  
Diastolic Function ◽  
Healthy Controls ◽  
Cross Sectional ◽  
Factors Associated ◽  
Youth Study ◽  
Hispanic White ◽  
Diabetes In Youth

Abstract Aims To compare left ventricular structure (LV) and diastolic function in young adults with youth- onset diabetes by type, determine the prevalence of abnormal diastolic function by diabetes type using published values from age similar healthy controls, and examine the risk factors associated with diastolic function. Methods In a cross sectional analysis we compared LV structure and diastolic function from two dimensional echocardiogram in participants with type 1 (T1D) and type 2 diabetes (T2D) who participated in the SEARCH for Diabetes in Youth Study. Linear models were used to examine the risk factors associated with worse diastolic function. Results Of 479 participants studied, 258 had T1D (mean age 21.2 ± 5.2 years, 60.5% non-Hispanic white, 53.9% female) and 221 had T2D (mean age 24.8 ± 4.3 years, 24.4% non-Hispanic white, 73.8% female). Median diabetes duration was 11.6 years. Participants with T2D had greater LV mass index and worse diastolic function that persisted after adjustment for differences in risk factors compared with participants with T1D (all p < 0.05). Abnormal diastolic function, quantified using healthy controls, was pronounced in both groups but greater in those with T2D than T1D (T2D: 57.7% vs T1D: 47.2%, respectively), p < 0.05. Risk factors associated with worse diastolic function included older age at diabetes diagnosis, female sex, higher BP, heart rate and HbA1c and longer diabetes duration. Conclusions LV structure and diastolic function is worse in individuals with T2D compared to T1D. However, abnormal diastolic function in seen in both groups compared to published values from age similar healthy controls.

Hypersomnolence Disorders

2020 ◽  
pp. 134-157
Author(s):  
Sulaiman Alhifzi ◽  
Nevin Zaki ◽  
Aljohara S. Almeneesier ◽  
Ahmed S. BaHammam
Keyword(s):  
Substance Use ◽  
Psychiatric Disorder ◽  
Treatment Strategies ◽  
Classification Systems ◽  
Common Symptom ◽  
Clinical Investigations ◽  
Idiopathic Hypersomnia ◽  
Multiple Sleep Latency

Despite varied classification systems, hypersomnolence disorders (or central disorders of hypersomnolence) are a group of disorders with a common symptom of excessive daytime sleepiness. In addition to a thorough clinical interview and examination, the assessment of hypersomnolence may require clinical investigations such as polysomnography and the multiple sleep latency test. This chapter examines the disorders of hypersomnolence with an emphasis on their clinical features and treatment strategies. The authors discuss the four main types of hypersomnolence disorders, narcolepsy type 1, narcolepsy type 2, idiopathic hypersomnia and Kleine–Levin syndrome, as well as hypersomnia due to a medical disorder, medication, or substance use; a psychiatric disorder; and insufficient sleep syndrome. It also discusses the relationships between hypersomnolence and psychiatric disorders.

VWF Binding to Types I, III or VI Collagen In the ZPMCB-VWD with Identification of Subjects with Selective Reduced Plasma VWF:CB

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 235-235
Author(s):  
Veronica H Flood ◽  
Sandra L Haberichter ◽  
Kenneth D Friedman ◽  
Steven R Lentz ◽  
Joan Cox Gill ◽  
...  
Keyword(s):  
Amino Acid ◽  
Type I ◽  
Healthy Controls ◽  
Type Vi Collagen ◽  
Collagen Binding ◽  
Type Iii ◽  
Type 3 ◽  
Von Willebrand

Abstract 235 Von Willebrand Disease (VWD) is a common bleeding disorder caused by quantitative (types 1 and 3) and qualitative (type 2) abnormalities in von Willebrand factor (VWF). Defective VWF binding to collagen (VWF:CB) has been identified in VWD patients, but the type(s) and amount of collagen vary between recommended assays. We measured VWF:CB using separate assays for types I, III, and VI collagen in plasmas from 233 healthy controls and 315 VWD index cases (261 type 1, 37 type 2 and 17 type 3) recruited into the Zimmerman Program for the Molecular and Clinical Biology of VWD (ZPMCB-VWD). Additional studies included VWF antigen (Ag), VWF ristocetin-cofactor (RCo), VWF multimer, and VWF gene sequence analysis. VWF:CB was tested using ELISA assays with type I human placental collagen (5 ug/ml), type III human placental collagen (1 ug/ml), and by a commercial human placental type VI VWF:CB assay (Technoclone, Austria). Normal ranges were established for VWF:CB and VWF:CB/Ag ratios with the ZPMCB-VWD healthy control population. Three subjects (2 healthy controls and 1 type 1 VWD subject) were identified with reduced VWF:CB and reduced VWF:CB/Ag ratios to type VI collagen, despite normal results with type I and type III collagen. The two control subjects had VWF:CB/Ag ratios of 0.43 and 0.51 for type VI collagen. The patient with type 1 VWD had absent type VI VWF:CB and a VWF:Ag of 54 IU/dL with a history of clinical epistaxis and an EU Bleeding Score of 8 (normal less than or equal to 3). VWF sequencing demonstrated that these three individuals had an A1 loop polymorphism, R1399H, which has been previously reported as a VWF polymorphism. No other individuals in our study had this sequence change. Of particular note was that the VWF:CB/Ag ratios for types I and III collagen were each normal – suggesting a selective abnormality. As anticipated, collagen binding with all collagens was undetectable in the type 3 VWD subjects. Type 2A and 2B VWD subjects demonstrated reduced VWF:CB and VWF:CB/Ag ratios to all three types of collagen. Type 2M and 2N VWD subjects exhibited normal VWF:CB/Ag ratios to all three types of collagen, but one type 2M patient with an I1425F A1 loop mutation had a reduced VWF:CB/Ag ratio of 0.58. In the VWF A1 domain crystal structure, amino acid 1425 is in close proximity to amino acid 1399, suggesting the conformation of that region may be critical to type VI collagen binding to VWF. Since the frequency of the R1399H polymorphism is estimated to be 2% of the population (Sadler and Ginsburg, 1993), defective binding to type VI collagen may be an important contributor to the variability in the bleeding phenotype of VWD. Disclosures: Lentz: Novo Nordisk: Consultancy. Montgomery:GTI Diagnostics, Inc: Consultancy.

scholarly journals Serum IL-17, IL-23, and TGF-βLevels in Type 1 and Type 2 Diabetic Patients and Age-Matched Healthy Controls

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Azam Roohi ◽  
Mina Tabrizi ◽  
Farzaneh Abbasi ◽  
Asal Ataie-Jafari ◽  
Behrouz Nikbin ◽  
...  
Keyword(s):  
Serum Levels ◽  
Diabetic Patients ◽  
Low Grade ◽  
Healthy Controls ◽  
Type 2 Diabetic Patients ◽  
Significant Difference ◽  
Type 1 Diabetic Patients ◽  
Type 2 Diabetic

Type 1 diabetes is recognized as an autoimmune inflammatory disease and low grade inflammation is also observed in type 2 diabetic patients. Interleukin 17 (IL-17) is a new player in inflammation. Th17 cells, as the main source of IL-17, require transforming growth factorβ(TGF-β) and interleukin 23 (IL-23). The aim of this study was to investigate serum IL-17, IL-23 and TGF-βlevels in diabetic patients and controls. In this case-control study, serum levels of IL-17, IL-23, and TGF-βwere measured in 24 type 1 diabetic patients and 30 healthy controls using the ELISA method. Simultaneously, the same methodology was used to compare serum concentration of these three cytokines in 38 type 2 diabetic patients and 40 healthy controls. There was no significant difference between serum levels of IL-17 and IL-23 cytokines between cases and controls. However, TGF-βwas significantly lower in type 1 diabetic patients (P<0.001). Serum IL-17 and IL-23 levels demonstrate no association with type 1 and type 2 diabetes, but, in line with previous studies, TGF-βlevels were lower in type 1 diabetic patients.

scholarly journals The impact of diabetes mellitus on the course and outcome of pregnancy during a 5-year follow-up

2014 ◽  
Vol 71 (10) ◽  
pp. 907-914 ◽  
Author(s):  
Milena Mitrovic ◽  
Sinisa Stojic ◽  
Dragan Tesic ◽  
Djordje Popovic ◽  
Olivera Rankov ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Gestational Diabetes ◽  
Preterm Delivery ◽  
Pregnancy Outcomes ◽  
Diabetes Type ◽  
Fetal Macrosomia ◽  
Healthy Controls ◽  
Healthy Women

Background/Aim. Women with diabetes, especially diabetes type 1, have worse pregnancy outcomes, as well as increased incidence of spontaneous abortions, pre-eclampsia, fetal macrosomia, preterm delivery, congenital anomalies and perinatal mortality. The aim of this study was to analyze the course and outcome of pregnancy in the patients with diabetes in relation to the group of healthy women regarding preterm delivery, perinatal morbidity and mortality. Also, the aim was to compare pregnancy outcomes in the patients with pre-existing diabetes type 1 and the patients with gestational and diabetes type 2. Methods. This retrospective study included 156 diabetic women treated at the Clinic of Endocrinology, Diabetes and Metabolic Diseases and Gynecology and Obstetrics Clinic of the Clinical Center of Vojvodina from 2006 to 2010. There were 94 patients with gestational diabetes, 48 with type 1 diabetes, and 14 patients with type 2 diabetes. The control group included 106 healthy women hospitalized at the Gynecology and Obstetrics Clinic. Results. The women with type 1 diabetes presented with a statistically significantly higher incidence of cesarean section than those without diabetes, or with type 2 or gestational diabetes (p < 0.0001); the women with type 1 diabetes delivered at an earlier week of gestation (WG) in regard to women without diabetes, or with type 2 or gestational diabetes (p = 0.0017 and p = 0.02, respectively). The incidence of perinatal morbidity: hypoglycemia (p < 0.001), pathological jaundice (p = 0.0021), and other neonatal pathologies at birth (p = 0.0031), was statistically significantly higher and Apgar scores after 1 minute (p = 0.0142) and after 5 minutes (p = 0.0003) were statistically significantly lower in the patients with diabetes compared to the healthy women. The women with type 2 and gestational diabetes were statistically significantly older than those with type 1 diabetes (p = 0.001). A higher incidence of fetal macrosomia in the women with gestational and type 2 diabetes compared to those with type 1 diabetes was at the borderline of statistical significance (p = 0.07), whereas the incidence of hypoglycemia of newborn was statistically significantly higher in the patients with type 1 diabetes (p < 0.0001). Glycosylated hemoglobin (HbA1c) levels were statistically significantly higher in the diabetic women giving birth during and before the week of gestation 36 (p = 0.0087), but there were no differences in HbA1c levels in regard to fetal macrosomia (p = 0.45) and congenital abnormalities (p = 0.32). Conclusion. The results of our study show a higher incidence of perinatal fetal morbidity (hypoglycemia, jaundice, respiratory distress syndrome) in the patients with type 1, type 2 and gestation diabetes than in the healthy controls. Also, we found a higher incidence of cesarean section in the patients with type 1 diabetes than in those with type 2, gestation diabetes and healthy controls. Although delivery in the patients with type 1, type 2 and gestational diabetes was completed approximately one to two weeks earlier compared to the healthy controls there was no statistically significant difference in the incidence of preterm delivery (? 36th week of gestation) between the women with diabetes and healthy controls. Preterm delivery associated with poorer glycaemic control reflected through higher values of HbA1c in third trimester. Risks from adverse pregnancy outcomes may be reduced to minimum by adequate preconception counseling of diabetic patients and early diagnosis of diabetes in pregnancy, in order to achieve glycemic control during organogenesis and within pregnancy and through the teamwork of endocrinologists, gynecologists and pediatricians.

scholarly journals Serum proteomics reveals systemic dysregulation of innate immunity in type 1 diabetes

2012 ◽  
Vol 210 (1) ◽  
pp. 191-203 ◽  
Author(s):  
Qibin Zhang ◽  
Thomas L. Fillmore ◽  
Athena A. Schepmoes ◽  
Therese R.W. Clauss ◽  
Marina A. Gritsenko ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Immune Responses ◽  
Innate Immune ◽  
Healthy Controls ◽  
Innate Immune Responses ◽  
C1 Inhibitor ◽  
Serum Samples ◽  
Healthy Control

Using global liquid chromatography-mass spectrometry (LC-MS)–based proteomics analyses, we identified 24 serum proteins that were significantly variant between those with type 1 diabetes (T1D) and healthy controls. Functionally, these proteins represent innate immune responses, the activation cascade of complement, inflammatory responses, and blood coagulation. Targeted verification analyses were performed on 52 surrogate peptides representing these proteins, with serum samples from an antibody standardization program cohort of 100 healthy control and 50 type 1 diabetic subjects. 16 peptides were verified as having very good discriminating power, with areas under the receiver operating characteristic curve ≥0.8. Further validation with blinded serum samples from an independent cohort (10 healthy control and 10 type 1 diabetics) demonstrated that peptides from platelet basic protein and C1 inhibitor achieved both 100% sensitivity and 100% specificity for classification of samples. The disease specificity of these proteins was assessed using sera from 50 age-matched type 2 diabetic individuals, and a subset of proteins, C1 inhibitor in particular, were exceptionally good discriminators between these two forms of diabetes. The panel of biomarkers distinguishing those with T1D from healthy controls and those with type 2 diabetes suggests that dysregulated innate immune responses may be associated with the development of this disorder.

scholarly journals Traditional biomarkers in narcolepsy: experience of a Brazilian sleep centre

2010 ◽  
Vol 68 (5) ◽  
pp. 712-715 ◽  
Author(s):  
Fernando Morgadinho Santos Coelho ◽  
Márcia Pradella-Hallinan ◽  
Mario Pedrazzoli ◽  
Carlos Augusto Senne Soares ◽  
Gustavo Bruniera Peres Fernandes ◽  
...  
Keyword(s):  
Cerebral Spinal Fluid ◽  
Sleep Latency ◽  
Sao Paulo ◽  
Spinal Fluid ◽  
Multiple Sleep Latency Test ◽  
São Paulo ◽  
Laboratory Findings ◽  
Multiple Sleep Latency ◽  
Hypocretin 1

This study was thought to characterized clinical and laboratory findings of a narcoleptic patients in an out patients unit at São Paulo, Brazil. METHOD: 28 patients underwent polysomnographic recordings (PSG) and Multiple Sleep Latency Test (MSLT) were analyzed according to standard criteria. The analysis of HLADQB1*0602 allele was performed by PCR. The Hypocretin-1 in cerebral spinal fluid (CSF) was measured using radioimmunoassay. Patients were divided in two groups according Hypocretin-1 level: Normal (N) - Hypocretin-1 higher than 110pg/ml and Lower (L) Hypocretin-1 lower than 110 pg/ml. RESULTS: Only 4 patients of the N group had cataplexy when compared with 14 members of the L group (p=0.0002). DISCUSSION: This results were comparable with other authors, confirming the utility of using specific biomarkers (HLA-DQB1*0602 allele and Hypocretin-1 CSF level) in narcolepsy with cataplexy. However, the HLADQB1*0602 allele and Hypocretin-1 level are insufficient to diagnose of narcolepsy without cataplexy.

Comorbidity between central disorders of hypersomnolence and immune-based disorders

Neurology ◽  
2016 ◽  
Vol 88 (1) ◽  
pp. 93-100 ◽  
Author(s):  
Lucie Barateau ◽  
Régis Lopez ◽  
Isabelle Arnulf ◽  
Michel Lecendreux ◽  
Patricia Franco ◽  
...  
Keyword(s):  
Family History ◽  
Autoimmune Diseases ◽  
Positive Family History ◽  
Autoinflammatory Disorders ◽  
Increased Risk ◽  
Idiopathic Hypersomnia ◽  
History Of ◽  
Adults And Children

Objective:To assess and compare the frequencies of personal and family history of autoimmune diseases (AID), autoinflammatory disorders (ID), and allergies in a population of patients, adults and children, with narcolepsy type 1 (NT1), narcolepsy type 2 (NT2), and idiopathic hypersomnia (IH), 3 central hypersomnia disorders, and healthy controls.Methods:Personal and family history of AID, ID, and allergies were assessed by questionnaire and medical interview in a large cohort of 450 consecutive adult patients (206 NT1, 106 NT2, 138 IH) and 95 pediatric patients (80 NT1) diagnosed according to the third International Classification of Sleep Disorders criteria in national reference centers for narcolepsy in France and 751 controls (700 adults, 51 children) from the general population.Results:Ten adults with NT1 (4.9%) had a comorbid AID vs 3.4% of adult controls, without between-group differences in adjusted models. AID frequency did not differ between children with NT1 and controls. Conversely, compared with controls, AID frequency was higher in adults with NT2 (p = 0.002), whereas ID (p = 0.0002) and allergy (p = 0.003) frequencies were higher in adults with IH. A positive family history of AID was found in the NT1 group and of ID in the IH group.Conclusions:NT1 is not associated with increased risk of comorbid immune disorders, in favor of a potentially unique pathophysiology. Conversely, compared with controls, the frequency of autoimmune diseases was higher in adults with NT2, whereas allergies and autoinflammatory disorders were more common in adults with IH, suggesting an immune dysregulation mechanism in these conditions.

PP116-MON DIETARY QUALITY IN PEOPLE WITH TYPE 1 AND TYPE 2 DIABETES COMPARED WITH HEALTHY CONTROLS

2013 ◽  
Vol 32 ◽  
pp. S165
Author(s):  
K.S. Petersen ◽  
N. Blanch ◽  
P.M. Clifton ◽  
J.B. Keogh
Keyword(s):  
Type 2 Diabetes ◽  
Dietary Quality ◽  
Healthy Controls
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