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Vascular Laboratory, Cairo University, Cairo, Egypt
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Hypothyroidism is associated with increased risk of atherosclerosis. We assessed carotid intima-media thickness (CIMT), as a marker of atherosclerosis, and endothelial function in patients with hypothyroidism. We included 70 female patients with hypothyroidism in the study, 40 patients with overt and 30 patients with subclinical hypothyroidism. Forty, age- and sex-matched, subjects with normal thyroid functions were also included as a control group. CIMT was measured using high-resolution color-coded Doppler ultrasonography. Endothelial function was assessed by measuring the percent of change in blood flow following heat-mediated vasodilation using laser Doppler flowmetry. CIMT was significantly higher in patients with overt and subclinical hypothyroidism as compared with the control group (0.7âÂąâ0.2 and 0.6âÂąâ0.2âmm respectively vs 0.45âÂąâ0.07âmm, Pâ<â0.001 for both). The percent of change in blood flow following heat-mediated vasodilation was significantly impaired in patients with overt and subclinical hypothyroidism as compared with the control group (328âÂąâ17 and 545âÂąâ406% respectively vs 898âÂąâ195%, Pâ<â0.001 for both). The impairment was more significant in overt as compared with subclinical hypothyroidism (Pâ=â0.014). CIMT negatively correlated with percent of change in blood flow following heat-mediated vasodilation in patients with overt and subclinical hypothyroidism (Pâ<â0.001 for both). We concluded that CIMT is significantly higher in patients with overt and subclinical hypothyroidism compared with normal control subjects. Impairment of endothelial function is a contributing factor to the increased risk of atherosclerosis in both groups of patients.
Search for other papers by Roxanne C S van Adrichem in
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To date, the value of fasting plasma acylated ghrelin (AG) and unacylated ghrelin (UAG) as potential novel biomarkers in patients with neuroendocrine tumors (NETs) is unknown. The aims of this study are to (i) compare fasting AG and UAG levels between nonobese, nondiabetic NET patients (N=28) and age- (Âą3 years) and sex-matched nonobese, nondiabetic controls (N=28); and (ii) study the relationship between AG, UAG, and AG/UAG ratios and biochemical (chromogranin-A (CgA) and neuron-specific enolase (NSE) levels) and clinical parameters (age at diagnosis, sex, primary tumor location, carcinoid syndrome, ENETS TNM classification, Ki-67 proliferation index, grading, prior incomplete surgery) in NET patients. Fasting venous blood samples (N=56) were collected and directly stabilized with 4-(2-aminoethyl) benzenesulfonyl fluoride hydrochloride after withdrawal. Plasma AG and UAG levels were determined by ELISA. Expression of ghrelin was examined in tumor tissue by immunohistochemistry. There were no significant differences between NET patients and controls in AG (median: 62.5 pg/mL, IQR: 33.1â112.8 vs median: 57.2pg/mL, IQR: 26.7â128.3, P=0.66) and UAG in levels (median: 76.6pg/mL, IQR: 35.23â121.7 vs median: 64.9, IQR: 27.5â93.1, P=0.44). No significant correlations were found between AG, UAG, and AG/UAG ratios versus biochemical and clinical parameters in NET patients with the exception of age at diagnosis (AG: Ď= â0.47, P=0.012; AG/UAG ratio: Ď= â0.50, P=0.007) and baseline chromogranin-A levels (AG/UAG ratio: Ď= â0.44, P=0.019). In our view, fasting plasma acylated and unacylated ghrelin appear to have no value as diagnostic biomarkers in the clinical follow-up of patients with NETs.
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Aim
In the present study, we investigated the long-term effects of exenatide treatment on serum fasting ghrelin levels in patients with type 2 diabetes mellitus.
Methods
Type 2 diabetic patients, who were using metformin with and without the other antihyperglycemic drugs on a stable dose for at least 3 months, were enrolled in the study. BMI>35âkg/m2 and HbA1c>7.0% were the additional inclusion criteria. Oral antihyperglycemic drugs, other than metformin, were stopped, and metformin treatment was continued at 2000âmg per day. Exenatide treatment was initiated at 5âÂľg per dose subcutaneously (sc) twice daily, and after one month, the dose of exenatide was increased to 10âÂľg twice daily. Changes in anthropometric variables, glycemic control, lipid parameters and total ghrelin levels were evaluated at baseline and following 12 weeks of treatment.
Results
Thirty-eight patients (male/femaleâ=â7/31) entered the study. The mean age of patients was 50.5âÂąâ8.8 years with a mean diabetes duration of 8.5âÂąâ4.9 years. The mean BMI was 41.6âÂąâ6.3âkg/m2 and the mean HbA1c of patients was 8.9âÂąâ1.4%. The mean change in the weight of patients was â5.6âkg and the percentage change in weight was â5.2âÂąâ3.7% following 12âweeks of treatment. BMI, fasting plasma glucose and HbA1c levels of patients were decreased significantly (Pâ<â0.001 and Pâ<â0.001; respectively), while there was no change in lipid parameters. Serum fasting ghrelin levels were significantly suppressed following 12 weeks of exenatide treatment compared with baseline values (328.4âÂąâ166.8 vs 245.3âÂąâ164.8âpg/mL) (Pâ=â0.024).
Conclusion
These results suggest that the effects of exenatide on weight loss may be related with the suppression of serum fasting ghrelin levels, which is an orexigenic peptide.
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Background:
Evidence has demonstrated that visceral fat area (VFA) and subcutaneous fat area (SFA) had different influences on cardiovascular disease (CVD) risk in patients with type 2 diabetes mellitus (T2DM). We aimed to investigate the relationship between the visceral fat area (VFA) to subcutaneous fat area (SFA) ratio (V/S) and carotid atherosclerosis (CAS) in patients with T2DM.
Methods:
From January 2018 to May 2023, 1,838 patients with T2DM admitted to the National Metabolic Management Centre in our hospital were assigned to two groups based on comorbid CAS. Dual bioelectrical impedance analysis was used to measure the VAF and SFA, and the V/S was calculated. Patient characteristics and serum biochemical indices were compared between groups. Factors influencing comorbid CAS were determined, and correlations between V/S and other clinical indices were analyzed.
Results:
The group with comorbid CAS included 858 individuals and 980 without comorbid CAS. Those with comorbid CAS were older and had a longer disease duration, more significant systolic blood pressure, and greater V/S. The proportions of patients with comorbid hypertension increased significantly with the V/S ratio. The V/S ratio positively correlated with triglyceride (TG), low-density lipoprotein cholesterol levels, and waist circumference. According to binary logistic regression analysis, V/S was an independent risk factor for CAS.
Conclusion:
Elevated V/S is an independent risk factor for CAS in patients with T2DM.
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Childhood obesity is associated with stress. However, most treatment strategies include only dietary and physical activity approaches. Mindfulness may assist in weight reduction, but its effectiveness is unclear. We assessed the effect of mindfulness on stress, appetite regulators, and weight of children with obesity and anxiety. A clinical study was conducted in a pediatric hospital. Eligible children were 10â14 years old, BMI âĽ95th percentile, Spence anxiety score âĽ55, and who were not taking any medication or supplementation. Participants were assigned to receive an 8-week conventional nutritional intervention (CNI) or an 8-week mindfulness-based intervention plus CNI (MND-CNI). Anthropometry, body composition, leptin, insulin, ghrelin, cortisol, and Spence scores were measured at baseline and at the end of the intervention. Anthropometry was analyzed again 8 weeks after concluding interventions. Log-transformed and delta values were calculated for analysis. Thirty-three MND-CNI and 12 CNI children finished interventions; 17 MND-CNI children accomplished 16 weeks. At the end of the intervention, significant reductions in anxiety score (â6.21âÂąâ1.10), BMI (â0.45âÂąâ1.2 kg/m2), body fat (â1.28âÂąâ0.25%), ghrelin (â0.71âÂąâ0.37 pg/mL), and serum cortisol (â1.42âÂąâ0.94 Âľg/dL) were observed in MND-CNI children. Changes in anxiety score, ghrelin, and cortisol were different between groups (Pâ<â0.05). Children who completed 16 weeks decreased BMI after intervention (â0.944âÂąâ0.20 kg/m2, Pâ<â0.001) and remained lower 8 weeks later (â0.706âÂąâ0.19 kg/m2, Pâ=â0.001). We concluded that mindfulness is a promising tool as an adjunctive therapy for childhood obesity. However, our findings need confirmation in a larger sample population.
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Pharmacokinetics of leptin in mammals has not been studied in detail and only one study has examined more than one time point in non-mutant mice and this was in a female mice. This is the first study to describe leptin distribution over a detailed time course in normal male mice. A physiologic dose (12âng) of radiolabelled leptin was injected into adult male mice via the lateral tail vein and tissues were dissected out and measured for radioactivity over a time course of up to two hours. Major targets were the digestive tract, kidneys, skin and lungs. The brain was not a major target, and 0.15% of the total dose was recovered from the brain 5âmin after administration. Major differences appear to exist in the distribution of leptin between the male and female mice, indicating a high degree of sexual dimorphism. Although the half-lives were similar between male and female mice, almost twice the proportion of leptin was recovered from the digestive tract of male mice in comparison to that reported previously for females. This would seem to indicate a major difference in leptin distribution and possibly function between males and females.
Search for other papers by Kristin Viste in
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Hormone Laboratory, Department of Medicine, Department of Clinical Science, Department of Radiology, Haukeland University Hospital, 5021 Bergen, Norway
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Hormone Laboratory, Department of Medicine, Department of Clinical Science, Department of Radiology, Haukeland University Hospital, 5021 Bergen, Norway
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Hormone Laboratory, Department of Medicine, Department of Clinical Science, Department of Radiology, Haukeland University Hospital, 5021 Bergen, Norway
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Primary aldosteronism (PA) is a common cause of secondary hypertension and is caused by unilateral or bilateral adrenal disease. Treatment options depend on whether the disease is lateralized or not, which is preferably evaluated with selective adrenal venous sampling (AVS). This procedure is technically challenging, and obtaining representative samples from the adrenal veins can prove difficult. Unsuccessful AVS procedures often require reexamination. Analysis of cortisol during the procedure may enhance the success rate. We invited 21 consecutive patients to participate in a study with intra-procedural point of care cortisol analysis. When this assay showed nonrepresentative sampling, new samples were drawn after redirection of the catheter. The study patients were compared using the 21 previous procedures. The intra-procedural cortisol assay increased the success rate from 10/21 patients in the historical cohort to 17/21 patients in the study group. In four of the 17 successful procedures, repeated samples needed to be drawn. Successful sampling at first attempt improved from the first seven to the last seven study patients. Point of care cortisol analysis during AVS improves success rate and reduces the need for reexaminations, in accordance with previous studies. Successful AVS is crucial when deciding which patients with PA will benefit from surgical treatment.
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Department of Gastroenterology, Turku University Hospital, Turku, Finland
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Department of Endocrinology, Turku University Hospital, Turku, Finland
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Aims/hypothesis
The mechanisms for improved glycemic control after bariatric surgery in subjects with type 2 diabetes (T2D) are not fully known. We hypothesized that dynamic hepatic blood responses to a mixed-meal are changed after bariatric surgery in parallel with an improvement in glucose tolerance.
Methods
A total of ten morbidly obese subjects with T2D were recruited to receive a mixed-meal and a glucose-dependent insulinotropic polypeptide (GIP) infusion before and early after (within a median of less than three months) bariatric surgery, and hepatic blood flow and volume (HBV) were measured repeatedly with combined positron emission tomography/MRI. Ten lean non-diabetic individuals served as controls.
Results
Bariatric surgery leads to a significant decrease in weight, accompanied with an improved β-cell function and glucagon-like peptide 1 (GLP-1) secretion, and a reduction in liver volume. Blood flow in portal vein (PV) was increased by 1.65-fold (Pâ=â0.026) in response to a mixed-meal in subjects after surgery, while HBV decreased in all groups (Pâ<â0.001). When the effect of GIP infusion was tested separately, no change in hepatic arterial and PV flow was observed, but HBV decreased as seen during the mixed-meal test.
Conclusions/interpretation
Early after bariatric surgery, PV flow response to a mixed-meal is augmented, improving digestion and nutrient absorption. GIP influences the post-prandial reduction in HBV thereby diverting blood to the extrahepatic sites.
FacultĂŠ de Chirurgie Dentaire, UniversitĂŠ de Toulouse III, Toulouse, France
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CHU de Toulouse, Laboratoire dâHĂŠmatologie, Toulouse, France
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FacultĂŠ de Chirurgie Dentaire, UniversitĂŠ de Toulouse III, Toulouse, France
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Estrogenâprogestin therapy was previously considered as the standard of care for managing bothersome symptoms associated with menopause, but it increases risks of breast cancer and of thromboembolism. The combination of conjugated estrogen (CE) with bazedoxifene (BZA) named tissue-selective estrogen complex (TSEC) was designed to minimize or even abrogate the undesirable effects on breast, while maintaining the beneficial effects such as prevention of osteoporosis and suppression of climacteric symptoms. The risk on thromboembolism associated with TSEC is unknown, although the clinical available data are reassuring. The aim of this study was to define the impact of a chronic administration of CE, BZA or CEâ+âBZA on hemostasis and thrombosis in ovariectomized mice. As expected, CE, but not BZA neither CEâ+âBZA, induced uterine and vagina hypertrophy. As previously demonstrated for 17β-estradiol (E2), we found that CE (i) increased tail-bleeding time, (ii) prevented occlusive thrombus formation in injured carotid artery and (iii) protected against collagen/epinephrine-induced thromboembolism. Thus, whereas BZA antagonized CE action on reproductive tissues, it had no impact on the effect of CE on hemostasis, thromboembolism and arterial thrombosis in mice. CEâ+âBZA shared the anti-thrombotic actions of CE in these mouse models. If a similar process is at work in women, CE combined with BZA could contribute to minimize the risk of thrombosis associated with hormone replacement therapy.
INSERM, University of Rouen, Department of Endocrinology, Departments of Endocrinology, Pathology, Department of Pathology, Department of Endocrinology, INSERM, U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedicine, MontâSaintâAignan, France
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INSERM, University of Rouen, Department of Endocrinology, Departments of Endocrinology, Pathology, Department of Pathology, Department of Endocrinology, INSERM, U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedicine, MontâSaintâAignan, France
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INSERM, University of Rouen, Department of Endocrinology, Departments of Endocrinology, Pathology, Department of Pathology, Department of Endocrinology, INSERM, U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedicine, MontâSaintâAignan, France
INSERM, University of Rouen, Department of Endocrinology, Departments of Endocrinology, Pathology, Department of Pathology, Department of Endocrinology, INSERM, U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedicine, MontâSaintâAignan, France
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INSERM, University of Rouen, Department of Endocrinology, Departments of Endocrinology, Pathology, Department of Pathology, Department of Endocrinology, INSERM, U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedicine, MontâSaintâAignan, France
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INSERM, University of Rouen, Department of Endocrinology, Departments of Endocrinology, Pathology, Department of Pathology, Department of Endocrinology, INSERM, U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedicine, MontâSaintâAignan, France
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Hirsutism induced by hyperandrogenism can be associated with polycystic ovary syndrome, 21-hydroxylase (OH) deficiency or androgen-secreting tumors, including ovarian and adrenal tumors. Adrenal androgen-secreting tumors are frequently malignant. Adrenal oncocytomas represent rare causes of hyperandrogenism. The aim of the study was to investigate steroidogenic enzyme expression and steroid secretion in an androgen-secreting adrenal oncocytoma in a young woman presenting with hirsutism. Hyperandrogenism was diagnosed on the basis of elevated plasma Î4-androstenedione and testosterone levels. Pelvic ultrasound was normal, CT scanning revealed a right adrenal mass. Androgens were assessed in adrenal and ovarian vein samples and proved a right adrenal origin. Adrenalectomy normalized androgen levels and the adrenal tumor was diagnosed as an oncocytoma. Real time-PCR, immunohistochemistry and cell culture studies were performed on tumor explants to investigate the steroid secretion profile. Among enzymes required for cortisol synthesis, 17Îą-OH and 3β-hydroxysteroid dehydrogenase 2 (3β-HSD2) were highly expressed whereas 21-OH and 11β-OH were weakly produced at the mRNA and/or protein levels. Enzymes involved in testosterone production, 17β-HSD5 and 17β-HSD3, were also detected. ACTH receptor was present in the tissue. Cortisol, Î4-androstenedione and testosterone secretions by cultured cells were increased by ACTH. These results provide the first demonstration, to our knowledge, of abnormal expression profile of steroidogenic enzymes in an adrenocortical oncocytoma. Our results also indicate that Î4-androstenedione hypersecretion resulted from high 17Îą-OH and 3β-HSD2 expression in combination with low expression of 21-OH and 11β-OH. Testosterone production was ascribed to occurrence of 17β-HSD5 and 17β-HSD3. Finally, our results indicate that androgen secretion was stimulated by ACTH.
