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 (706 kJ) 10 min long at 0800 h, 0900 h, 1000 h and 1100 h. 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 10 min after meal initiation (P<0.0001): +20.9±5.8 and +10.7±3.3 pg/ml in normal-weight and obese subjects for the first meal; +10.4±3.0 and +5.5±3.9 pg/ml in normal-weight and obese subjects for the second meal; +12.4±3.6 and +4.2±2.1 pg/ml in normal-weight and obese subjects for the third meal; and +4.4±4.1 and +3.3±2.61 pg/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?

AIM: This study aimed to determine whether third-trimester adipokines during gestational diabetes (GDM) are associated with higher metabolic risk. METHODS: A 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. RESULTS: Pre-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. CONCLUSION: Diagnosing 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).

Recent advances in the characterization of hair of mummies from the Chilean Andean coast.

Two pre-Hispanic mummies from the Andean coast, belonging to a corpus of 16 mummies from the San Miguel de Azapa (Arica, Chile), were radiocarbon dated and analyzed in order to replace them in their historical context and to study the conservation state of the hair fibers and the heavy metal presence. The radiocarbon dating placed both mummies in the Formative period (1700 years BC to 500 years AD). Global and elemental analyses were performed using scanning electron microscopy coupled with energy dispersive X-ray spectroscopy and using X-ray fluorescence spectroscopy. These combined techniques enabled to prove the good global conservation state of the mummies' hair and to detect iron, lead, bromide and also arsenic in some cases, in significant amounts inside the hair fibers. Fourier transformed infra-red spectroscopy seemed to prove the good conservation state of the hair surface at a structural level that is why the conservation of hair proteins at a molecular level will be investigated by a proteomics approach in future work.

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

AIM: This 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. METHODS: Plasma 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. RESULTS: TSH 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. CONCLUSION: Our 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.

Good practice guide for cervical ultrasound scan and echo-guided techniques in treating differentiated thyroid cancer of vesicular origin.

Good practice guide for cervical ultrasound scan and echo-guided techniques in treating differentiated thyroid cancer of vesicular origin. American, European and French Recommendations for the treatment of differentiated vesicular thyroid cancer were recently published. Cervical ultrasound scanning is now considered a key examination in the follow-up of these cancers. This examination is noninvasive, easy to perform and to obtain, is not costly, but remains operator-dependent. To date, there are no recommendations published that assemble all the technical aspects, results, indications and the limits of this examination in the initial medical report and the follow-up of these cancers. In order to standardise the procedure and validate the quality of the examination, a workgroup made up of a panel of experts particularly involved in carrying out ultrasound scans was set up. The aim was to draw up a good practice guide for performing cervical ultrasound scans and echo-guided techniques in treating patients with differentiated thyroid cancer of vesicular origin. The main objectives are to: (a) standardise the procedure and reports, (b) define the criteria for establishing whether lesions identified during a cervical ultrasound scan are malignant or benign, (c) standardise the indications for carrying out cytological tests and an in situ assay of markers, (d) help doctors to select the patients who ought to receive a cervical ultrasound scan and or cytological tests, (e) discuss how frequently the examinations should be carried out depending on the risk of recurrence.

Comparison of metabolic deterioration between insulin analog and regular insulin after a 5-hour interruption of a continuous subcutaneous insulin infusion in type 1 diabetic patients.

An interruption of continuous sc insulin infusion (CSII) of the insulin analog lispro should result in a more rapid metabolic deterioration of type 1 diabetic patients because of its pharmacokinetic characteristics. We analyzed the metabolic changes occurring during a 5-h interruption of CSII and the 5 h after restarting the pump in 10 type 1 diabetic patients. The study was a randomized, cross-over, open label design comparing insulin analog [Lispro (LP)] and regular insulin [Velosuline (VE)]. Plasma glucose, free insulin, glucagon, betahydroxybutyrate (beta-OHB), and nonesterified fatty acids (NEFA) were measured every hour from 0700 h (time zero) to 1700 h (600 min). After stopping CSII, the plasma glucose level was significantly higher in the LP group than in the VE group (P < 0.05-0.01). The plasma free insulin level decreased significantly with the two treatments, but was significantly lower with LP than with VE (P < 0.05-0.01). Plasma NEFA increased more rapidly and was significantly higher in the LP group than in the VE group (P < 0.01-0.05). Plasma beta-OHB increased earlier with LP, but was not statistically different between the treatments. After restarting the pump, plasma glucose decreased with LP, but continued to increase with VE, and the plasma free insulin peak occurred earlier and was greater with LP than with VE (P < 0.05). Plasma NEFA and beta-OHB levels decreased significantly with the two treatments, but more dramatically with LP treatment. Thus, a short interruption of Lispro in CSII is associated with an earlier, greater metabolic deterioration, but Lispro corrected this metabolic deterioration more effectively.

[Analytical evaluation of third generation TSH assay. Application to the exploration of thyrotropin suppression in differentiated thyroid cancer]. / Evaluation analytique d'un dosage de TSH de troisième génération. Application à l'exploration du freinage thyréotrope des cancers thyroïdiens différenciés.

Intravenous TRH (200 micrograms Protiréline) injection was performed in 137 patients who had undergone thyroidectomy for differentiated thyroid carcinoma and treated by a suppressive thyroid therapy. Serum thyroid stimulating hormone (TSH) was measured before and 30 minutes after the injection. 143 tests were performed. The TSH method used was a chemiluminometric assay (Chiron Diagnostics). We study the analytical characteristics of the method. The limit of detection was 0.003 mUI/l. Interassay precision showed a functional sensitivity of 0.015 m UI/l with 20% interassay CV in agreement with the third generation criterion. There was a good correlation between TSH values at T0 and T30 minutes. In 143 tests, 40 (28%) showed a basal TSH value less than 0.003 mUI/l; delta TSH (TSH at T30-TSH at T0) was less than 0.015 mUI/l in about 68% of the cases and less than 0.031 mUI/l for the others. In 20% of the tests (29) TSH T0 were between 0.003 and 0.015 mUI/l and delta TSH less than 0.204 mUI/l. Finally the 74 remaining tests with a basal TSH value higher than the functional sensitivity of the method showed delta TSH less than 0.4 mUI/l if the TSH T0 was less than 0.05 mUI/l. The delta TSH remained less than 0.6 mUI/l if the TSH T0 was less than 0.1 mUI/l. Inversely, if TSH T0 was higher than 0.1 mUI/l delta TSH could be higher than 1.0 mUI/l. Third generation TSH assay allows us to abandon TRH test for the follow-up of thyroidectomized patients with suppressive thyroid hormonotherapy in so far as TSH assay is well established. We conclude that a basal TSH less than the functional sensitivity (0.015 mUI/l) can predict a TSH response to TRH stimulation test less than 0.2 mUI/l.

Massive weight loss does not restore normal insulin secretory pulses in obese patients with type 2 (non-insulin-dependent) diabetes mellitus.

To study the effects of massive weight loss on insulin secretion, we analysed the oscillations of fasting peripheral insulin levels in obese patients who underwent vertical banded gastroplasty as treatment for morbid obesity. Patients were studied before and 6 months after surgery. Serial measurements of plasma free insulin levels were obtained in duplicates from 0 to 60 min at one-minute intervals. Insulin levels were then analysed by autocorrelation and Fourier transformation. In normal controls and obese patients, the first oscillatory insulin component was detected between 10 and 14 min. Compared to obese controls (n = 4), overt Type 2 diabetic patients (n = 4) had reduced amplitudes of insulin pulses and no oscillatory component. These defects were not as pronounced in patients with impaired glucose tolerance (IGT) after an oral glucose tolerance test (OGTT) (n = 5). When detected, the periodicity of the oscillations occurred at different periods. In 3/5 IGT patients, the first positive peak of correlation was found at 13.3 +/- 2.3 min. Weight loss (mean +/- SD) after 6 months was 24.3 +/- 3.7 for subjects with normal glucose tolerance (NGT), 37.9 +/- 9 for those with IGT and 29.8 +/- 5 kgs for Type 2 diabetic subjects. After weight loss, insulin oscillatory activity was detected in 4/5 IGT patients, with a period of 13 +/- 3 min. Weight loss did not reverse the defects observed in obese diabetic patients despite a significant reduction in peripheral insulin levels from 28.6 +/- 6 to 15.6 +/- 6 mU/l (p < 0.05). Insulin values remained higher than in obese controls (7.82 +/- 2, p < 0.05), and Type 2 patients remained mildly hyperglycaemic. These findings indicate that beta-cell activity is abnormal in Type 2 diabetic patients. The absence of modification after weight loss suggests that inherent beta-cell defects may contribute to hyperglycaemia.

[Rapid peroperative assay of intact parathormone in primary hyperparathyroidism. Evaluation and comparison with the long method]. / Dosage per-opératoire rapide de la parathormone intacte dans l'hyperparathyroïdie primaire. Evaluation et comparaison avec la méthode longue.

OBJECTIVES: To evaluate the efficacy of rapid peroperative assay of parathormone in patients with primary hyperparathyroidism compared with the longer standard assay. METHODS: Primary hyperthyroidism was diagnosed in 10 patients (8 males, 2 females, mean age 55 +/- 8.6 years, range 36-99) (preoperative tests: serum calcium 290 +/- 8.9 nmol/l, range 274-311; intact parathormone 137 +/- 31.3 pg/ml, range 87-250). First intention cervicotomy was performed. Blood samples were drawn at induction of anaesthesia, at palpation of the adenoma, and 15, 30 and 45 minutes after ablation. Each sample was assayed with a rapid radioimmunoassay and the longer standard laboratory methods. RESULTS: There was a good correlation between the two assay methods. In the 9 patients with a solitary adenoma, serum levels of parathormone were normalized 15 (n = 8) or 30 minutes (n = 1) after resection. CONCLUSION: Rapid radioimmunoassay is a reliable method for evaluating serum parathormone level peroperatively. Although financial implications may limit its use, this rapid assay is clearly indicated for patients in poor clinical condition undergoing first intention surgery and in those undergoing a second cervicotomy.

[Insulin secretion in nondiabetic manioc consumers]. / L'insulinosécrétion des consommateurs de manioc non diabétiques.

The study of pancreatic beta cell function during an intravenous glucose tolerance test performed on 28 healthy cassava eaters showed 3 types of response: normal insulin secretion in 17 subjects, a significantly elevated peak at 30 min, compared to the control group (6 subjects p less than 0.0125), with preservation of insulin secretion dynamics, and a late peak at 120 min. (5 subjects p less than 0.0125). Among the different factors capable of stimulating insulin secretion, in absence of a significant increase in glycaemia, the hypothesis of cell membrane lesions caused by cyanogenic components has been suggested. The abnormalities observed seem to be in relation with the length of duration of cassava consumption, but neither with plasmatic or urinary levels of thiocyanate, nor with the genetic study.

[Inverse relationship between body mass index and fasting insulinemia with testosterone-binding protein in hirsutism]. / Relation inverse de l'index de masse corporelle et de l'insulinémie à jeun avec la protéine de liaison de la testostérone au cours de l'hirsutisme.

To identify the factor(s) involved in the decreased of sex steroid binding-protein (SBP) in hirsute women, we have investigated which parameters were in correlation with SBP in a population of 90 hirsute women. We found no significant correlation of SBP binding capacity with the plasma concentrations of the main androgens. Conversely, SBP was in inverse and significant correlation with body mass index and with the fasting insulin plasma level. These findings confirm that nutritional status must be considered in the physiopathology of hyperandrogenism in women. The control of overweight may be a goal for treating hirsutism in some patients.

[C-peptide assays of the urine and plasma at baseline and under stimulation with glucagon in healthy subjects and diabetics]. / Dosages du C-peptide urinaire et plasmatique de base et sous stimulation par le glucagon chez des sujets sains ou diabétiques.

Urinary (CPU) and plasma C peptide values at baseline (CP0) and under stimulation with glucagon were determined in healthy subjects (n = 17) and in insulin-dependent (IDD, n = 45) and non insulin-dependent (NIDD, n = 32) diabetics. A significant difference in the parameters of insulin secretion (x? SD) was found on the one hand between the IDD group (CPU = 5.58 +/- 5.58 nmol/24 h; CP = 0.14 +/- 0.08 nmol/l; maximum C peptide value after stimulation (CPmax) = 0.33 +/- 0.31 nmol/l; C peptide delta (delta CP) = 0.14 +/- 0.14 nmol/l; area under the curve (A) = 5.00 +/- 4.84) and the NIDD group (CPU = 15.47 +/- 8.22 nmol/24 h; CP = 0.64 +/- 0.28 nmol/l; CPmax = 1.14 +/- 0.44 nmol/l; delta CP = 0.50 +/- 0.31 nmol/l; A = 17.5 +/- 5.86) and on the other hand between the IDD group and the control group (CPU = 18.20 +/- 8.40 nmol/24 h; CP = 0.41 +/- 0.11 nmol/l; CPmax = 1.00 +/- 0.31 nmol/l; delta CP = 0.69 +/- 0.20 nmol/l; A = 17.10 +/- 4.45). As regards the NIDD group, only the fasting C peptide and delta C peptide values were significantly different from those found in the control group. The significance of each parameter of insulin secretion was also studied. There was a correlation between the values of C peptidaemia before and after stimulation with glucagon. However, the correlation between plasma C peptide and urinary C peptide values was mediocre, probably because of the numerous variability factors which intervene in the urinary excretion of C peptide.

[Discrepancy between the basal level of TSH and the thyrotropic response to TRH during thyroid hormone treatment of differentiated thyroid cancers]. / Discordance entre dosage basal de TSH et réponse thyréotrope à TRH au cours du traitement par les hormones thyroïdiennes des cancers thyroïdiens différenciés.

Serum TSH (Thyroid Stimulating Hormone) was measured before and 30 minutes after a 200 microgram intravenous TRH (Protiréline*) injection in 270 patients. These patients have been treated for one year at least, by a suppressive thyroid therapy after thyroidectomy for a differentiated thyroid carcinoma. 314 tests were performed. We used an ultrasensitive TSH method (Ciba-Corning-Diagnostics). The normal range (mean :1.68 mUI/l; range: 0.45 to 3.80 mUI/l) was determined in 116 euthyroid patients. Minimal response to TRH was studied in 35 untreated patients with hyperthyroidism (TSH TO: less than 0.30 mUI/l and delta TSH: less than 0.09 mUI/l). There was a relationship (r = 0.916) between TSH response 30 minutes after TRH stimulation (T30) and basal TSH value: in a logarithmic scale (fitting of the data by a bi-gaussian model). TRH tests were classified too, by basal TSH values (TO) and delta TSH (TSH at T30-TSH at TO). In 201 tests in which TO TSH was less than 0.30 mUI/l (maximal value in hyperthyroidism), 50 showed a delta TSH higher than 0.15 mUI/l (25% of the cases) and in 6 cases (3%), delta TSH was even higher than 2.0 mul/l; in 67 of the 75 tests (89.3%) where TSH TO is less than 0.15 mUI/l, delta TSH is no (less than 0.15 mUI/l). In 93 tests where TO TSH was upper than 0.45 mUI/l (minimal value in euthyroidism), delta TSH was higher than 2.0 mUI/l in 87 cases (93.6%).(ABSTRACT TRUNCATED AT 250 WORDS)

Increased luteinizing hormone sensitivity to dopaminergic inhibition in Graves' disease.

The effect of dopamine infusion (4 micrograms X kg-1 X min-1 from 9.00 to 13.00 h) on serum LH and FSH concentrations were studied in 15 patients (10 women, 5 men) with diffuse toxic goitre, and 10 healthy subjects (6 women, 4 men). Basal serum LH (17.0 +/- 0.8 IU/l) and oestradiol (women: 3.74 +/- 1.84; men: 3.05 +/- 0.77 pmol/l) were elevated in patients, whereas serum FSH and PRI were normal. Dopamine infusion did not modify serum FSH levels, but significantly depressed LH concentration in both hyperthyroid and healthy subjects. The LH decrement was more pronounced (P less than 0.01) in patients with Graves' disease (8.4 +/- 1.4 IU/l) as compared with controls (2.3 +/- 0.9 IU/l). There was a positive correlation between the maximum net decrease and the basal LH concentration (r = 0.95). The per cent decrease of LH levels in the hyperthyroid patients (54 +/- 4) was higher (P less than 0.001) than that in the controls. The finding of enhanced sensitivity to dopamine inhibition in thyrotoxic patients suggests that their inappropriately elevated serum LH levels may result in part from a reduced dopaminergic inhibition of LH secretion.