Free triiodothyronine (T3) is negatively associated with fasting ghrelin serum levels in a population sample of euthyroid subjects.

PURPOSE: Ghrelin is an orexigenic peptide hormone secreted in times of stress and hunger. It is deeply involved in the regulation of metabolism and energy homeostasis, promoting energy intake and inhibiting energy expenditure on a metabolic level. In this regard, it has in many ways antagonistic effect on the thyroid hormones, which increase metabolism and thus energy expenditure. While there is reasonable evidence of a negative association between ghrelin and hormones of the hypothalamic-pituitary-thyroid (HPT-) axis from studies in patients with thyroid dysfunction and small intervention studies, large-scale studies in healthy subjects are lacking. Therefore, we studied the relationship between total ghrelin serum levels and serum levels of the thyroid hormones in a large sample of euthyroid subjects. METHODS: Total ghrelin, thyroid-stimulating hormone (TSH), free thyroxine (fT4) and free triiodothyronine (fT3) were determined after an overnight fast in 1666 subjects participating in a population-based cross-sectional study ('LIFE') including 10,000 adults. 1012 subjects were included in this analysis. Multiple linear regression analyses were performed. RESULTS: FT3 was negatively associated with serum ghrelin; total sample: ß = - 0.0001, p < 0.001; men: ß = - 0.0002, p = 0.013; women: ß = - 0.0001, p = 0.010, adjusted for age, BMI, alcohol consumption, serum levels of TSH and fT4 and smoking status. No associations were found between ghrelin serum levels and serum levels of fT4 or TSH. CONCLUSION: This is to date the largest study investigating the relationship between total serum ghrelin and thyroid hormones. The results point to a complex interaction and should initiate further research.

Serum BDNF levels correlate with regional cortical thickness in minor depression: a pilot study.

Serum brain-derived neurotrophic factor (BDNF) reflects state changes in mood disorders. But its relation to brain changes in depression has rarely been investigated in humans. We assessed the association between serum BDNF, cortical thickness, or gray matter volume in 20 subjects with a minor depressive episode and 40 matched healthy subjects. Serum BDNF positively correlated with cortical thickness and volume in multiple brain regions in the minor depression group: the bilateral medial orbitofrontal cortex and rostral anterior cingulate cortex, left insula, and cingulum, right superior frontal gyrus, and other regions-regions typically affected by major depression. Interestingly, these correlations were driven by subjects with first episode depression. There was no significant association between these imaging parameters and serum BDNF in the healthy control group. Interaction analyses supported this finding. Our findings point to a specific association between serum BDNF and magnetic resonance imaging parameters in first-episode minor depression in a region- and condition-dependent manner. A positive correlation between serum BDNF and structural gray matter estimates was most consistently observed for cortical thickness. We discuss why cortical thickness should be preferred to volumetric estimates for such analyses in future studies. Results of our pilot study have to be proven in future larger-scale studies yielding higher statistical power.

Internalized weight bias and cortisol reactivity to social stress.

Weight-associated stigmatization and discrimination may induce chronic stress in individuals with obesity. As a consequence, this stressor may cause an imbalance of HPA stress axis leading to increased eating behavior, and ultimately, weight gain. However, the direct link between internalized weight bias and stress response to acute stressors via cortisol secretion has not been investigated so far. Therefore, the purpose of this study was to investigate the interaction between internalized weight stigma as a stressor and cortisol reactivity in an acute psychosocial stress situation induced by the Trier Socials Stress Test for groups (TSST-G). Participants with BMI >30 kg/m2 (n = 79) were included in the study. Results reveal that while individuals with low internalized stigma reacted as predicted with an increase in cortisol secretion to acute psychosocial stress, individuals with medium or high internalized stigma did not show a typical cortisol response. However, these findings depend on the several factors, for instance on gender. In sum, acute stress in individuals with internalized weight bias seems to blunt HPA axis reactions to acute psychosocial stress. The study contributes to the understanding of the psychological and endocrinological consequences of internalized weight bias and underlines the importance of interventions to reduce stigmatization.

Children and adolescents with obesity have reduced serum bone turnover markers and 25-hydroxyvitamin D but increased parathyroid hormone concentrations - Results derived from new pediatric reference ranges.

BACKGROUND: We aimed to establish age- and gender-specific reference ranges for concentrations of the bone markers osteocalcin (OC), procollagen type 1 N-propeptides (PINP) and carboxy-terminal cross-linking telopeptide of type 1 collagen (CTX-I) as well as for the calciotropic hormones 25-hydroxyvitamin D [25(OH)D] and parathyroid hormone (PTH) in healthy infants, children and adolescents. In addition, the effect of age, gender, puberty and body mass index (BMI) on bone markers was investigated. METHODS: 2416 healthy subjects (5714 blood withdrawals), aged 3 months to 17 years, were included to estimate the age- and gender-dependence of reference ranges. Subsequently, measured values of the biomarkers were transformed to standard deviation scores (SDS) and their associations with age, gender and puberty were analyzed. Bone marker-SDS values of the reference cohort were compared with an obese cohort (n = 317 and 489 blood withdrawals) to analyze the effect of BMI. RESULTS: OC, PINP and CTX-I showed a distinct age- and gender-dependence with peak levels at 10 to 11 years (girls, Tanner 3) and 13 years (boys, Tanner 3-4). Children with obesity had significantly lower SDS levels for OC (-0.44), PINP (-0.27), CTX-I (-0.33), 25(OH)D (-0.43) and higher SDS levels for PTH (+0.44) than the reference cohort. CONCLUSIONS: OC, PINP and CTX-I vary with age, gender and pubertal stage. The body weight status has to be considered in the interpretation of pediatric OC, PINP, CTX-I, 25(OH)D and PTH levels. Consequences of childhood obesity on bone health should be carefully investigated in long-term studies.

Circulating Pro-Neurotensin in gestational diabetes mellitus.

BACKGROUND AND AIMS: Pro-Neurotensin (NT), a stable surrogate parameter of NT, has recently been introduced as a peptide predicting the development of obesity, diabetes mellitus, cardiovascular diseases, and cardiovascular mortality. However, regulation of Pro-NT in gestational diabetes mellitus (GDM) remains uninvestigated. METHODS AND RESULTS: Pro-NT was quantified in 74 women with GDM, 74 healthy, gestational age-matched, pregnant controls, as well as in a second cohort comprising of 74 healthy, non-pregnant control women, using a chemiluminometric sandwich immunoassay. Pro-NT was correlated to measures of obesity, hypertension, glucose and lipid metabolism, renal function, and inflammation. Mean ± standard deviation of circulating Pro-NT levels were not significantly different in women with GDM (100.2 ± 75.7 pmol/l) as compared to healthy, pregnant controls (103.2 ± 37.4 pmol/l) and healthy, non-pregnant female controls (105.9 ± 38.9 pmol/l) (p = 0.661). Homeostasis model assessment of insulin resistance (HOMA-IR) and creatinine positively correlated with serum Pro-NT in multivariate regression analysis. In contrast, free fatty acids (FFA) were inversely correlated with circulating Pro-NT. Results sustained adjustment for pregnancy status. CONCLUSIONS: Circulating Pro-NT is not independently associated with GDM, but is with HOMA-IR, creatinine, and FFA even after adjustment for pregnancy status.

The brown-fat-secreted adipokine neuregulin 4 is decreased in gestational diabetes mellitus.

AIMS: Neuregulin 4 has recently been recognized as a novel adipokine secreted by brown adipose tissue (BAT), with beneficial effects on murine insulin resistance and hepatic steatosis. Yet, thus far, neither regulation of neuregulin 4 in gestational diabetes mellitus (GDM) nor its longitudinal changes in the peripartum period have been elucidated. METHODS: Circulating neuregulin 4 levels were measured by ELISA in 74 women with GDM and 74 healthy, gestational-age-matched controls. Also, neuregulin 4 was quantified during pregnancy and compared with postpartum levels in a follow-up study of 25 women with previous GDM and 25 healthy control women. RESULTS: Women with GDM had lower median serum levels of the novel BAT-secreted adipokine neuregulin 4 (3.0µg/L) compared with healthy (non-GDM) pregnant controls (3.5µg/L; P=0.020), and the area under the glucose curve (AUCGlucose) was an independent and negative predictor of circulating neuregulin 4 (P=0.033). Also, median postpartum serum concentrations of neuregulin 4 (3.2µg/L) were not significantly different from prepartum levels (2.8µg/L; P=0.328). In addition, neuregulin 4 was positively and independently associated with irisin (P=0.009), but not other BAT-secreted adipokines. CONCLUSION/INTERPRETATION: Women with GDM have significantly lower circulating neuregulin 4 levels compared with healthy pregnant controls, and the AUCGlucose is negatively and independently associated with neuregulin 4 during pregnancy. Neuregulin 4 is positively correlated with irisin during pregnancy, as well as in a longitudinal fashion. Future studies are now needed to better elucidate the precise pathomechanisms of the regulation of BAT-secreted adipokines during pregnancy.

Adipocyte C1QTNF5 expression is BMI-dependently related to early adipose tissue dysfunction and systemic CTRP5 serum levels in obese children.

BACKGROUND/OBJECTIVES: The recently identified adipocytokine C1QTNF5 (encodes for CTRP5) has been demonstrated to inhibit pro-metabolic insulin signaling in adipocytes. We hypothesized that adipocyte C1QTNF5 expression in subcutaneous (sc) adipose tissue (AT) would correlate with the degree of obesity, systemic CTRP5 serum levels, and early AT and metabolic dysfunction in children. SUBJECTS/METHODS: Sc AT samples were obtained from 33 healthy Caucasian lean children aged 10.06±4.84 years and 42 overweight and obese children aged 13.34±3.12 years. C1QTNF5 expression in sc AT as well as in investigated cell lines was assessed by quantitative real-time PCR. Systemic CTRP5 levels were assessed by ELISA. RESULTS: C1QTNF5 expression in sc adipocytes increased with body mass index (BMI) standard deviation score (SDS; R=0.48, P<0.001), body fat percentage (R=0.4, P=0.004), adipocyte number (R=0.69, P<0.001) and systemic CTRP5 serum levels (R=0.28, P=0.025) whereas expression in the stromal vascular fraction (SVF) was inversely correlated with BMI SDS (R=-0.24, P=0.04). Multiple regression analysis confirmed that BMI SDS was the strongest independent predictor for C1QTNF5 expression in sc adipocytes. SVF C1QTNF5 levels strongly correlated with SVF CD31 expression (R=0.54, P<0.001) indicating expression by endothelial cells. Primary human endothelial cells demonstrated stronger expression compared with human Simpson-Golahbi-Behmel syndrome pre-adipocytes and adipocytes. Adipocyte C1QTNF5 expression levels were BMI-dependently related to fasting insulin (R=0.3, P=0.03) and leptin serum levels (R=0.5, P<0.001). Sc AT samples containing crown-like structures (CLS) demonstrated increased adipocyte C1QTNF5 expression compared to CLS-negative samples (P=0.03). Functionally, tumor necrosis factor (TNF)α caused a fourfold induction of C1QTNF5 in human adipocytes (P<0.001) and a 50% reduction in primary human endothelial cells (P<0.001). CONCLUSIONS: In children adipocyte C1QTNF5 expression is already strongly related to the degree of obesity and is associated with obesity-related AT alterations, systemic CTRP5 serum levels as well as circulating markers of metabolic disease and is positively regulated by TNFα in vitro.

Nicotinamide phosphoribosyltransferase production in human spermatozoa is influenced by maturation stage.

High amounts of nicotinamide phosphoribosyltransferase (NAMPT) were found in human seminal plasma. This enzyme influences energy metabolism and apoptosis and is essential for the regulation of cellular nicotinamide adenine dinucleotide (NAD)+ levels in somatic cells. NAD+ is required as a co-substrate for dehydrogenases, which are potentially important for spermatogenesis. The functional significance of intra- and extracellular NAMPT in human reproduction, however, has not been defined yet. The objectives of the study were therefore to determine NAMPT protein expression in human spermatozoa and testes, the secretion of NAMPT by spermatozoa depending on their maturation stage and the impact of NAMPT enzymatic function on sperm viability, motility, fertilisation capacity and induction of apoptosis. Firstly, we detected NAMPT protein in different cell types of human testes. NAMPT protein was also detected in spermatozoa, with significantly higher amounts in immature than in mature ejaculated spermatozoa. Additionally, NAD+ levels were significantly higher in immature than in mature spermatozoa. Secondly, NAMPT was released into the supernatant of human spermatozoa, with significantly higher NAMPT levels in supernatant of immature spermatozoa compared with mature cells. Finally, the specific inhibition of the enzyme by FK866 did not influence motility, capacitation or apoptosis signalling. In summary, NAMPT is produced in human spermatozoa in a maturation-dependent manner.

HBsAg and anti-HCV screening in elderly hospitalized patients of a German tertiary referral centre.

BACKGROUND: Elderly patients are under-represented in hepatitis B and C screening approaches, but may be at increased risk for advanced liver disease. We therefore screened a hospitalized elderly population. MATERIALS AND METHODS: 6011 admissions to the department of internal medicine and neurology within one year were screened for HBsAg and anti-HCV (Elecsys(®)-HBsAg and -anti-HCV). Positive anti-HCV results were confirmed with the INNO-LIA™ assay. HCV-RNA was analyzed by real-time PCR in the case of confirmed positive anti-HCV results, HBV-DNA in the confirmed HBsAg positive individuals. RESULTS: Patient´s mean age (62.4 years) was 19 years above that of the average German population. The confirmed HBsAg prevalence was 0.6 %. 34 % (n = 12/35) of HBsAg positive cases were newly diagnosed, three of them presented with HBV-DNA levels > 2000 IU/mL. The confirmed anti-HCV prevalence was 0.9 %. 14 % (n = 8/56) of anti-HCV positive patients were previously undiagnosed. HCV-RNA was positive in three of them. In newly diagnosed individuals cirrhosis was present in 1/12 of the HBsAg and in 3/8 of the anti-HCV positive individuals. Compared to non-infected controls, the following risk factors were significantly more frequent in infected patients: (i) HBsAg: sexual exposure (20 % vs. 2 %), blood transfusion before 1992 (13 % vs. 6 %), referrals from nursing homes (10 % vs. 1 %). (ii) Anti-HCV: blood transfusion before 1992 (41 % vs. 6 %), IVDU (25 % vs. 0.5 %), organ transplantation (20 % vs. 5 %), hemodialysis (11 % vs. 3 %). CONCLUSIONS: HBsAg and anti-HCV were underdiagnosed in a senescent population, however, only few cases presented with advanced liver disease. Referrals from nursing homes were at increased risk for HBV infection.

Gestational and Non-gestational Trophoblastic Disease. Guideline of the DGGG, OEGGG and SGGG (S2k Level, AWMF Registry No. 032/049, December 2015).

Purpose: The aim was to establish an official interdisciplinary guideline, published and coordinated by the German Society of Gynecology and Obstetrics (DGGG). The guideline was developed for use in German-speaking countries. In addition to the Germany Society of Gynecology and Obstetrics, the guideline has also been approved by the Swiss Society of Gynecology and Obstetrics (SGGG) and the Austrian Society of Gynecology and Obstetrics (OEGGG). The aim was to standardize diagnostic procedures and the management of gestational and non-gestational trophoblastic disease in accordance with the principles of evidence-based medicine, drawing on the current literature and the experience of the colleagues involved in compiling the guideline. Methods: This s2k guideline represents the consensus of a representative panel of experts with a range of different professional backgrounds commissioned by the DGGG. Following a review of the international literature and international guidelines on trophoblastic tumors, a structural consensus was achieved in a formalized, multi-step procedure. This was done using uniform definitions, objective assessments, and standardized management protocols. Recommendations: The recommendations of the guideline cover the epidemiology, classification and staging of trophoblastic tumors; the measurement of human chorionic gonadotropin (hCG) levels in serum, and the diagnosis, management, and follow-up of villous trophoblastic tumors (e.g., partial mole, hydatidiform mole, invasive mole) and non-villous trophoblastic tumors (placental site nodule, exaggerated placental site, placental site tumor, epitheloid trophoblastic tumor, and choriocarcinoma).

Associations between serum 25-hydroxyvitamin D and bone turnover markers in a population based sample of German children.

Severe vitamin D deficiency is known to cause rickets, however epidemiological studies and RCTs did not reveal conclusive associations for other parameters of bone health. In our study, we aimed to investigate the association between serum levels of 25(OH) vitamin D and bone turnover markers in a population-based sample of children. 25(OH)D, calcium (Ca), osteocalcin (OC), and ß-Crosslaps (ß-CTx) were measured in 2798 ten-year-old children from the German birth cohorts GINIplus and LISAplus. Linear regression was used to determine the association between bone turnover markers and 25(OH)D levels. 25(OH)D, OC, and ß-CTx showed a clear seasonal variation. A 10 nmol/l increase in 25(OH)D was significantly associated with a 10.5 ng/l decrease (p < 0.001) in ß-CTx after adjustment for design, sex, fasting status, time of blood drawn, BMI, growth rate, and detectable testosterone/estradiol. For OC alone no significant association with 25(OH)D was observed, whereas the ß-CTx-to-OC ratio was inversely associated with 25(OH)D (-1.7% change, p < 0.001). When stratifying the analyses by serum calcium levels, associations were stronger in children with Ca levels below the median. This study in school-aged children showed a seasonal variation of 25(OH)D and the bone turnover markers OC and ß-CTx. Furthermore a negative association between 25(OH)D and the bone resorption marker ß-CTx was observed.

Effects of a short-term reduction in brain serotonin synthesis on the availability of the soluble leptin receptor in healthy women.

Serotonin (5-HT) and the hormone leptin have been linked to the underlying neurobiology of appetite regulation with evidence coming from animal and cellular research, but direct evidence linking these two pathways in humans is lacking. We examined the effects of reduced brain 5-HT synthesis due to acute tryptophan depletion (ATD) on levels of soluble leptin receptor (sOb-R), the main high-affinity leptin binding protein, in healthy adults using an exploratory approach. Women, but not men, showed reduced sOb-R concentrations after ATD administration. With females showing reduced baseline levels of central 5-HT synthesis compared to males diminished brain 5-HT synthesis affected the leptin axis through the sOb-R in females, thereby potentially influencing their vulnerability to dysfunctional appetite regulation and co-morbid mood symptoms.

Experts' Opinion on the Prenatal Therapy of Congenital Adrenal Hyperplasia (CAH) Due to 21-Hydroxylase Deficiency - Guideline of DGKED in cooperation with DGGG (S1-Level, AWMF Registry No. 174/013, July 2015).

Purpose: This guideline of the German Society of Pediatric Endocrinology and Diabetology (DGKED) is designed to be experts' opinion on the current concept of prenatal therapy for congenital adrenal hyperplasia due to 21-hydroxylase deficiency (CAH). Several scientific medical societies have also participated in the guideline. It aims to offer guidance to physicians when they counsel affected families about prenatal therapy. Methods: The experts commissioned by the medical societies developed a consensus in an informal process. The consensus was subsequently confirmed by the steering committees of the respective medical societies. Recommendations: Prenatal CAH therapy is an experimental therapy. We recommend designing and using standardized protocols for the prenatal diagnosis, therapy and long-term follow-up of women and children treated prenatally with dexamethasone. If long-term follow-up is not possible, then prenatal therapy should not be performed.

Breast milk leptin and adiponectin in relation to infant body composition up to 2 years.

BACKGROUND: Adipokines in breast milk have been associated with infant growth trajectories. OBJECTIVE: We aimed to explore the relationship of leptin and adiponectin in breast milk with infant weight gain and body composition up to the age of 2 years. METHODS: Breast milk samples were collected from exclusively or partially breastfeeding mothers at 6 weeks (n = 152) and 4 months (n = 120) post-partum. Leptin and adiponectin were determined in skim breast milk and related to infant growth and fat mass assessed by skin-fold thickness measurements. A total of 118 infants were examined at 2 years. RESULTS: The levels of both milk adipokines were slightly lower at 4 months compared with 6 weeks post-partum. Breast milk leptin was largely unrelated to infant anthropometric measures up to 2 years. Milk adiponectin tended to be inversely related to early infant anthropometry up to 4 months, but beyond was positively associated with weight gain and the sum of skin-folds up to 2 years. CONCLUSIONS: Our results suggest that higher adiponectin levels in breast milk might be associated with greater weight gain and higher fat mass in the offspring up to 2 years.

Elevated serum 25(OH)-vitamin D levels are negatively correlated with molar-incisor hypomineralization.

To date, the precise etiology of molar-incisor hypomineralization (MIH) is uncertain. Vitamin D plays a key role in hard tissue formation. Therefore, this study aimed to analyze the relationship between serum 25-hydroxy-vitamin D (25(OH)D) status and dental health data obtained from 1,048 children in a 10-year follow-up of the Munich GINIplus and LISAplus birth cohorts. The dental examination included the diagnosis of MIH and recording of (non-)cavitated caries lesions in primary and permanent teeth. Serum 25(OH)D concentrations were taken from blood samples of the 10-year investigation and measured with a fully automated, modular system. Different logistic regression and Poisson hurdle models were calculated. MIH was diagnosed in 13.6% of the study population. Approximately 16.4% of the children demonstrated caries-related defects (D3-4MFS > 0). The mean season-adjusted concentration of 25(OH)D was 75.8 nmol/l (standard deviation 22.0 nmol/l). After adjusting for sex, age, body mass index, parental education, equivalent income, and television/personal computer (TV/PC) viewing hours, a 10 nmol/l increase in serum 25(OH)D concentrations was significantly associated with a lower odds ratio of having MIH (OR = 0.89; P = 0.006). Furthermore, higher 25(OH)D values were associated with a lower number of caries-affected permanent teeth. It is concluded that elevated serum 25(OH)D concentrations were associated with better dental health parameters.

[Thyroid dysfunction in pregnancy]. / Schilddrüsenfunktionsstörungen in der Schwangerschaft.

Thyroid dysfunction may impair fertility, course of pregnancy and fetal development. Physiological alterations of thyroid function parameters, that occur during pregnancy need to be distinguished from pathophysiological states of hypo- and hyperthyroidism. We performed a literature search (PubMed 1990-2013) and review relevant publications as well as consensus and practice guidelines of international thyroid/endocrine societies. Interpretation of thyroid function values in pregnancy must be based on trimester-specific TSH and T4 ranges. Alterations in thyroid function are present in up to 15% of pregnancies (0.4% overt hypothyroidism, 0.1-0.4% hyperthyroidism) and may lead to preventable complications in the pregnant woman and the fetus. Hypothyroidism is associated with an increased risk for abortion, premature delivery and stillbirth, besides impairment of neurocognitive development. The latter has also been shown in situations of grave iodine deficiency. In addition to new-born screening directed at early recognition of congenital hypothyroidism (incidence 0.03%), universal screening of all pregnant women should be implemented in health care guidelines. Newly diagnosed overt hypothyroidism in a pregnant woman requires immediate levothyroxine substitution at adequate doses. In subclinical hypothyroidism thyroid hormone replacement should be considered. Iodine supplementation is strongly recommended in all pregnant and breast-feeding women. Pregnancy causes a number of, that need to be of thyroid dysfunction. Both hypothyroidism and thyrotoxicosis may impair the course of pregnancy and may negatively affect the fetus. In particular, maternal hypothyroidism may lead to irreparable and detrimental deficits in the neurocognitive development of the fetus. Autoimmune thyroid disease is the most common cause of thyroid dysfunction in pregnancy. Hashimoto's thyroiditis is associated with impaired fertility and miscarriage, and may first manifest in pregnancy due to the increased thyroid hormone requirement. Graves' disease often shows a characteristic course in pregnancy with amelioration of thyrotoxicosis in the second half of pregnancy and exacerbation after delivery. In addition transplacental passage of maternal TSH receptor antibodies may lead to thyrotoxicosis in the fetus and/or newborn.

Circulating angiopoietin-like protein 8 is independently associated with fasting plasma glucose and type 2 diabetes mellitus.

OBJECTIVE: Angiopoietin-like protein 8 (Angptl8) has recently been introduced as a novel adipokine/hepatokine that promotes pancreatic ß-cell proliferation and improves glucose tolerance in mouse models of insulin resistance. However, regulation of Angptl8 in human type 2 diabetes mellitus (T2DM) and renal dysfunction has not been determined. RESEARCH DESIGN AND METHODS: Serum Angptl8 levels were quantified by ELISA in 62 patients with T2DM as compared with 58 nondiabetic subjects in vivo. Within both groups, about half of the patients were on chronic hemodialysis or had an estimated glomerular filtration rate above 50 mL/min/1.73 m(2). Furthermore, we investigated the effect of insulin and differentiation on Angptl8 mRNA expression in 3T3-L1 adipocytes in vitro. RESULTS: Median [interquartile range] serum Angptl8 levels were higher in patients with T2DM (1.19 [0.37] µg/L) as compared with nondiabetic subjects (1.03 [0.47] µg/L) (P = .005). Furthermore, the adipokine/hepatokine was significantly higher in women (1.21 [0.47] µg/L) as compared with men (1.05 [0.44] µg/L]) (P = .013). In multivariate analysis, fasting glucose and T2DM but not renal function remained independent and positive predictors of circulating Angptl8 even after adjustment for markers of obesity, lipid status, and inflammation (P < .05). Furthermore, Angptl8 mRNA expression was induced by insulin and during adipogenesis in 3T3-L1 adipocytes in vitro. CONCLUSIONS: Circulating Angptl8 is positively and independently associated with T2DM and fasting glucose in vivo. Furthermore, Angptl8 mRNA expression is induced by insulin and during adipogenesis in 3T3-L1 adipocytes in vitro.

Clinical evidence-based cutoff limits for GH stimulation tests in children with a backup of results with reference to mass spectrometry.

CONTEXT: Cutoff limits of GH stimulation tests to diagnose GH deficiency (GHD) in children and adolescents are not sufficiently validated by clinical studies due to discrepancies in the performance of GH immunoassays and lack of available study populations. OBJECTIVE: We aimed to establish new cutoff limits for GH stimulation tests based on clinical evidence and compared these immunoassay-based values with an antibody-independent mass spectrometric method. DESIGN AND SETTING: In a retrospective study, GH cutoff limits for eight different immunoassays and isotope dilution mass spectrometry (ID-MS) were calculated from hGH peak concentrations of short-statured children with and without GHD. PATIENTS: We compared the serum GH peak concentrations at GH stimulation test of 52 short-statured children and adolescents, who have normal GH secretion at initial workup and normal growth in the follow-up, with the serum GH peak concentrations of 44 GHD patients in the same age range, in order to optimize the cutoff limit calculation. RESULTS: Discriminant analysis of re-measured GH led to a new cutoff limit of 7.09 µg/l using the iSYS assay (IDS) and the limits for the other seven hGH assays varied between 4.32 and 7.77 µg/l. For ID-MS, cutoffs of 5.48 µg/l (22k GH) and 7.43 µg/l (total GH) were ascertained. CONCLUSION: The establishment of method-specific clinical evidence-based GH cutoff limits is of importance to ensure adequate clinical diagnosis and treatment of children and adolescents with GHD. ID-MS may become an important tool for providing both reliable and sustainable SI traceability of GH measurements in the future.