Anne Charrié

The relationship between adipokines, osteocalcin and bone quality in chronic kidney disease

OBJECTIVESnOsteocalcin, a small peptide secreted by osteoblasts, has been recently described as a circulating hormone involved in the regulation of energy metabolism. In addition, experimental data suggest a regulation of adipocytes by bone, with a stimulation of adiponectin synthesis by osteocalcin and an inverse relationship between serum adiponectin level and bone mineral density (BMD). However, this relationship has not been explored during chronic kidney disease (CKD).nnnMETHODSnOsteocalcin, adiponectin and leptin were prospectively measured in a cohort of 61 CKD patients. A new non-invasive 3D bone imaging technique was performed (high-resolution peripheral quantitative computed tomography, HR-pQCT), measuring volumetric BMD (vBMD) and microarchitecture parameters at the distal tibia.nnnRESULTSnPatients mean age was 67.2 +/- 13.9 years and mean GFR 33 +/- 12 mL/min/1.73 m(2). We found a positive association between serum osteocalcin and adiponectin (r = 0.29, P = 0.021). Univariate analysis showed inverse correlations between serum adiponectin and total vBMD (r = -0.33, P = 0.01), cortical thickness (r = -0.34, P = 0.008) and trabecular vBMD (r = -0.27, P = 0.04). These associations remained significant in multivariate analysis between serum adiponectin and total vBMD, cortical vBMD and cortical thickness.nnnCONCLUSIONnWe report for the first time an inverse relationship between bone density and adiponectin, as well as a positive association between osteocalcin and adiponectin in CKD II-IV patients.

Thyroglobulin measurement in fine-needle aspirates of lymph nodes in patients with differentiated thyroid cancer: a simple definition of the threshold value, with emphasis on potential pitfalls of the method.

Abstract Background: Thyroglobulin measurements in fine-needle aspirate (FNA-Tg) is an accurate method for the diagnosis of lymph node metastasis in differentiated thyroid carcinoma. The goal of this study is to determine the most appropriate diagnostic threshold value for FNA-Tg. Methods: Ultrasound-guided fine-needle aspiration-cytology (FNA-C) and FNA-Tg were performed on suspicious lymph nodes in 114 consecutive patients with thyroid cancer prior to thyroidectomy (n=13) or during follow-up (n=93), and in 16 control subjects. Functional sensitivity of the thyroglobulin assay was 0.7 ng/mL. Sensitivity and specificity of FNA-Tg and FNA-C were determined for different cut-off values within a range of 0.69–1.34 nanogram/punction (ng/p) using receiver operating characteristic curve analysis. Results: The FNA-Tg cut-off value of 0.93 ng/p offers the best diagnostic performances: 94.2% sensitivity, 97.8% specificity. FNA-C showed 100% specificity in diagnostic samples, but low sensitivity of 71% due primarily to inadequate samples. Combining FNA-C and FNA-Tg resulted in 98% sensitivity and 100% specificity. Conclusions: A unique threshold of 0.93 ng/p gives high sensitivity and specificity, even in non-thyroidectomized patients. However, since false negative results may be observed in poorly differentiated thyroid cancer, FNA-C should remain combined to FNA-Tg. Clin Chem Lab Med 2010;48:1171–7.

An isocaloric increase of eating episodes in the morning contributes to decrease energy intake at lunch in lean men

The effects of increasing eating frequency on human health are unclear. This study used an integrated approach to assess the short-term consequences on appetite and metabolism. Twenty normal-weight men participated in: (i) two sessions consisting of a breakfast consumed in one eating episode at T0 (F1), or in four isocaloric eating episodes at T0, T60, T120, and T180 min (F4), and followed by an ecological ad libitum buffet meal (T240) designed in an experimental restaurant. Intakes were assessed for the whole buffet meal and for each temporal quarter of the meal. (ii) two sessions consisting of the same two breakfasts F1 and F4 in a Clinical Investigation Centre. Blood sampling was performed to study the kinetics of ghrelin, glucagon-like peptide-1 (GLP-1), glucose, insulin, triglycerides and non-esterified fatty acids (NEFA). Substrate oxidation was measured by indirect calorimetry. During each of the 4 sessions, participants rated their appetite throughout the experiment. After F4, at T240 min, GLP-1 concentration was higher (P=0.006) while ghrelin concentration and hunger ratings were lower (P<0.001). We showed a trend for subjects to consume less energy (-88±61 kcal, P=0.08) at the buffet after F4, explained by a decrease in lipid intake (P=0.04). Marked differences in consumption were observed during the last temporal quarter of the meal for total energy and lipid intake (P=0.03). Mixed models highlighted differences between F1 and F4 for the kinetics of glucose, insulin and NEFA (P<0.001). The area under the curve was lower for insulin (P<0.001) and NEFA in F4 (P=0.03). Diet induced thermogenesis was reduced in F4 (P<0.05). This study demonstrated the beneficial short-term effect of increasing eating frequency on appetite in lean men considering subjective, physiological and behavioral data. However, the loss of the inter-prandial fast was associated with an inhibition of lipolysis, reflected by NEFA profiles, and a decrease in energy expenditure.

Effects of a breakfast spread out over time on the food intake at lunch and the hormonal responses in obese men.

The effects of frequent eating on health and particularly on appetite and metabolism are unclear. We have previously shown that frequent eating decreased appetite and energy intake at the subsequent meal in lean men. In the present study, we tested the same pattern in obese subjects. Seventeen obese men participated in: (i) two sessions consisting of a breakfast consumed in one eating episode at T0 (F1), or in four isocaloric eating episodes at T0, T60, T120, and T180min (F4), followed by an ad libitum buffet (T240) in an experimental restaurant. Subjects rated their appetite throughout the sessions. (ii) two sessions consisting of the same breakfasts F1 and F4 in a Clinical Centre, followed by a standardized meal. Blood sampling was performed to study ghrelin, glucagon-like peptide-1 (GLP-1), and metabolic kinetics. Indirect calorimetry measurements were performed. After F4, at T240min, ghrelin concentration (P=0.03) and hunger ratings (P<0.001) were lower while GLP-1 concentration (P=0.006) and satiety ratings (P=0.02) were higher. In F4, subjects consumed at the buffet, less food in grams (P=0.04) and less energy from low energy dense foods (P=0.01), but total energy intakes were not different between conditions. In F4, the area under the curve was lower for insulin (P=0.02) and non-esterified fatty acids (NEFA) (P=0.03). Diet induced thermogenesis was reduced in F4 (P=0.03) between T0 and T240. Even if subjective and physiological data suggest a beneficial effect of frequent eating on appetite in obese men, no effect was demonstrated on energy intake. Moreover, the decrease in diet induced thermogenesis and lipolysis, reflected by NEFA profiles, could be deleterious on energy balance in the long run.

Is basal ultrasensitive measurement of calcitonin capable of substituting for the pentagastrin‐stimulation test?

To evaluate a second‐generation assay for basal serum calcitonin (CT) measurements compared with the pentagastrin‐stimulation test for the diagnosis of inherited medullary thyroid carcinoma (MTC) and the follow‐up of patients with MTC after surgery. Recent American Thyroid Association recommendations suggest the use of basal CT alone to diagnose and assess follow‐up of MTC as the pentagastrin (Pg) test is unavailable in many countries.

Thyroxin overdose due to rheumatoid factor interferences in thyroid-stimulating hormone assays

Abstract Background: Immunoassays are susceptible to interferences by anti-hormone antibodies, heterophilic antibodies or rheumatoid factor (RF). Methods: We report a case of levothyroxin overdose because of gross overestimation of thyroid-stimulating hormone (TSH) by chemiluminescent and IRMA assays. Alternate assays were performed and heterophilic antibodies blocking tubes were used. Results: Analytical investigations revealed: i) non-linear concentrations of TSH after serum dilutions, ii) decreased TSH concentrations after removal of heterophilic antibodies, iii) appropriately decreased TSH concentrations in alternate TSH assays and iv) identification of increased concentrations of RF. Conclusions: The presence of RF may be responsible for false determination of TSH concentrations preventing monitoring of TSH.

Increased TSH in obesity: Evidence for a BMI-independent association with leptin

AIMnThis study aimed to determine whether the association between thyroid-stimulating hormone (TSH) and body mass index (BMI) is related to leptin concentration in obese individuals.nnnMETHODSnPlasma TSH and leptin assays were performed in 800 consecutive patients, hospitalized for a nutritional checkup, with a BMI ≥ 30 kg/m(2). Various anthropometric, hormonal and metabolic parameters, including age, weight, BMI, insulin, leptin and TSH, were measured or calculated. Univariate and multivariate regression analyses were performed to identify any significant relationships between these parameters. Also, characteristics of the patients in the lowest and highest quartiles of TSH distribution were compared.nnnRESULTSnTSH was positively correlated with both BMI and leptin. When multiple regression analysis was performed, TSH and leptin maintained a significant association independent of BMI. Patients in the fourth quartile of TSH distribution displayed higher BMI and higher leptin levels in comparison to the first quartile.nnnCONCLUSIONnOur study has confirmed an increase in TSH in conjunction with BMI in obese subjects. This increase was correlated with leptin independently of BMI. It is hypothesized that the increase in TSH observed in obese subjects was the consequence of both fat mass accumulation and a positive energy-balance.

Fast test: Clinical practice and interpretation ☆ ◊

Arnaud Agin b, Anne Charrie c, Karim Chikh c, Antoine Tabarin d, Delphine Vezzosi a,∗ a Service d’endocrinologie, maladies métaboliques et nutrition, centre hospitalier universitaire Rangueil-Larrey, université Paul Sabatier et Inserm U1037 Toulouse, 31059 Toulouse cedex 09, France b Unité mixte de recherche 7004, centre national de la recherche scientifique, institut de physique biologique, faculté de médecine, université Louis-Pasteur, 67000 Strasbourg, France c Laboratoire de technique nucléaire et biophysiques, centre hospitalier Lyon-Sud, 69495 Pierre-Bénite, France d Service d’endocrinologie-diabétologie et maladies métaboliques, hôpital Haut-Lévêque, GH Sud, CHU de Bordeaux, 33604 Pessac cedex, France

Plasma acyl-ghrelin increases after meal initiation: a new insight.

Background/Objectives:Plasma ghrelin secretion over time in humans is characterized by pre-prandial increases and by post-prandial decreases all day long. However, some authors who measured ghrelin concentrations around meals showed a rise in plasma ghrelin concentration after meal initiation followed by the typical post-prandial decrease. In order to confirm this observation that has never been discussed, we described ghrelin profiles around four eating episodes in the morning in adult men.Subjects/Methods:Twenty normal-weight and 17 obese men were instructed to eat four fixed meals (706u2009kJ) 10u2009min long at 0800u2009h, 0900u2009h, 1000u2009h and 1100u2009h. Using frequent blood sampling, we determined plasma acyl-ghrelin concentrations around those eating episodes. Glucose, insulin and GLP-1 concentrations were also measured.Results:The meals consumption induced a significant increase in plasma acyl-ghrelin concentrations 10u2009min after meal initiation (P<0.0001): +20.9±5.8 and +10.7±3.3u2009pg/ml in normal-weight and obese subjects for the first meal; +10.4±3.0 and +5.5±3.9u2009pg/ml in normal-weight and obese subjects for the second meal; +12.4±3.6 and +4.2±2.1u2009pg/ml in normal-weight and obese subjects for the third meal; and +4.4±4.1 and +3.3±2.61u2009pg/ml in normal-weight and obese subjects for the fourth meal.Conclusions:This study is the first to describe and discuss the post-meal initiation ghrelin increase. This finding is consistent in normal-weight and obese individuals.

Are third-trimester adipokines associated with higher metabolic risk among women with gestational diabetes?

AIMnThis study aimed to determine whether third-trimester adipokines during gestational diabetes (GDM) are associated with higher metabolic risk.nnnMETHODSnA total of 221 women with GDM (according to IADPSG criteria) were enrolled between 2011/11 and 2013/6 into a prospective observational study (IMAGE), and categorized as having elevated fasting blood glucose (FBG) or impaired fasting glucose (IFG, n = 36) if levels were ≥ 92 mg/dL during a 75-g oral glucose tolerance test (OGTT), impaired glucose tolerance (IGT, n = 116) if FBG was < 92 mg/dL but with elevated 1-h or 2-h OGTT values, or impaired fasting and stimulated blood glucose (IFSG, n = 69) if both FBG was ≥ 92 mg/dL and 1-h or 2-h OGTT values were elevated.nnnRESULTSnPre-gestational body mass index (BMI) was higher in women with IFG or IFSG compared with IGT (P < 0.001), as were leptin levels in women with IFG vs IGT [34.7 (10.5-119.7) vs 26.6 (3.56-79.4) ng/L; P = 0.008]. HOMA2-IR scores were higher in women with IFG or IFSG vs IGT (1.87 ± 1.2 or 1.72 ± 0.9 vs 1.18 ± 0.8, respectively; P < 0.001). Also, those with IFSG vs those with IGT had significantly lower HOMA2-B scores (111.4 ± 41.3 vs 127.1 ± 61.6, respectively; P < 0.05) and adiponectin levels [5.00 (1.11-11.3) vs 6.19 (2.11-17.7) μg/mL; P < 0.001], and higher levels of IL-6 [1.14 (0.33-20.0) vs 0.90 (0.31-19.0); P = 0.012] and TNF-α [0.99 (0.50-10.5) vs 0.84 (0.45-11.5) pg/mL; P = 0.003]. After adjusting for age, parity, and pre-gestational and gestational BMI, the difference in adiponectin levels remained significant.nnnCONCLUSIONnDiagnosing GDM by IADSPG criteria results in a wide range of heterogeneity. Our study has indicated that adipokine levels in addition to FBG may help to select women at high metabolic risk for appropriate monitoring and post-delivery interventions (ClinicalTrials.gov number NCP02133729).