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Open access

Charlotte Höybye, Laia Faseh, Christos Himonakos, Tomasz Pielak, and Jesper Eugen-Olsen

Growth hormone deficiency (GHD) syndrome is associated with adverse levels of several risk factors for cardiovascular diseases (CVD), including metabolic inflammation. However, the impact of GHD and GH treatment on low-grade inflammation is unknown. The aim of the study was to establish the level of the low-grade inflammation biomarker soluble urokinase plasminogen activator receptor (suPAR) in adults with GHD and the response to long-term GH treatment. Measurements of suPAR and CRP were performed in bio-bank serum samples from 72 adults, 34 males and 38 females, with GHD before and during at least 5 years of GH treatment. Mean age was 52.5 ± 15.5 years, BMI 27.3 ± 5 kg/m2. Clinical evaluations and blood sampling were performed at routine visits. Data on demography, anthropometry, lab results and clinical events were retrieved from post-marketing surveillance study databases and medical records. suPAR and high-sensitive (hs) CRP were analysed using ELISA and immunochemistry, respectively. At baseline blood pressure, lipid profile and fasting glucose were within the normal reference range. Baseline geometric mean and 95% CI of suPAR was 2.9 (2.7–3.3) ng/mL and of CRP 2.3 (0.6–4.0) mg/L. Mean follow-up was 8 ± 2 years. The suPAR levels remained stable during follow-up, although individual increases were seen on occurrence or presence of co-morbidities. In contrast, levels of CRP decreased. In conclusion, the decrease in CRP and indirectly the absence of an expected increase in suPAR over time indicates a favourable effect of GH on low-grade inflammation.

Open access

Valeria Hirschler, Claudia Molinari, Silvia Lapertosa, Gustavo Maccallini, and Claudio D Gonzalez

Background

The association between central obesity and cardiometabolic complications justifies exploring its association in normal-weight and overweight/obese (OW/OB) schoolchildren.

Objective

To describe cardiometabolic markers in four groups according to BMI/WC categories: (i) normal weight with central OB; (ii) normal weight without central OB; (iii) OW/OB with central OB and (iv) OW/OB without central OB, in a sample of Argentinean schoolchildren.

Methods

A cross-sectional study of 1264 Argentinean schoolchildren (624 F), aged 9.5 ± 2.2 years was performed between November 2013 and 2015. Children’s anthropometric measures, blood pressure (BP), glucose, lipids, and insulin were measured. Children were divided into four groups: (i) normal weight with central OB; (ii) normal weight without central OB; (iii) OW/OB with central OB and (iv) OW/OB without central OB.

Results

The prevalence of normal-weight children without central OB was 64.3% (796), normal weight with central OB 5% (66), OW/OB without central OB 11% (137), and OW/OB with central OB 21% (265). Normal weight with central OB had significantly higher triglycerides than normal-weight children without central OB (86 vs 70 mg/dL, respectively) and OW/OB children without central OB (81 vs 77 mg/dL). Multiple linear regression analyses showed that age, systolic BP, HDL-C, triglycerides, and maternal WC were significantly associated with children’s WC; R2 = 0.50 as well as children’s BMI; R2 = 0.37.

Conclusion

This study found that children with central OB might be at future higher cardiometabolic risk than those without central OB independently of the presence of OW/OB. However, future longitudinal studies should be performed to confirm these findings.

Open access

Xiaomin Nie, Yiting Xu, Xiaojing Ma, Yun Shen, Yufei Wang, and Yuqian Bao

Background

A high level of free triiodothyronine (FT3) within the reference range may be a potential metabolic risk marker. However, the relationship between different fat depots and FT3 has remained unclear.

Objective

We aimed to explore the relationships between segmental fat distribution and FT3 in euthyroid middle-aged and elderly men and postmenopausal women.

Methods

A total of 891 subjects (394 men and 497 women) were enrolled. A bioelectrical impedance analyzer was used to measure total, trunk, arm and leg fat mass (FM) and fat percentage (fat%). The leg fat mass to trunk fat mass ratio (LTR) was calculated to evaluate the relative distribution of leg fat compared with that of trunk fat. Thyroid hormones were measured by electrochemical luminescence immunoassay.

Results

FT3 in men did not change significantly with increases in LTR quartiles, while FT3 in women decreased significantly (P for trend = 0.004). In multivariate linear regression analysis, multiple metabolic and cardiovascular risk factors were adjusted. The LTR was negatively related to FT3 in women (P < 0.05). After further mutual adjustment for trunk fat and leg fat parameters, trunk FM and fat% were positively related to FT3, while leg FM and fat% were negatively related to FT3 in women (all P < 0.05).

Conclusions

In euthyroid postmenopausal women, trunk fat was positively correlated with FT3, whereas leg fat was negatively correlated with FT3. Our findings supported that a high level of FT3 within the reference range was related to adverse fat distribution.

Open access

Katica Bajuk Studen and Marija Pfeifer

Polycystic ovary syndrome (PCOS) is a common disorder in women of reproductive age. Besides hyperandrogenism, oligomenorrhea and fertility issues, it is associated with a high prevalence of metabolic disorders and cardiovascular risk factors. Several genetic polymorphisms have been identified for possible associations with cardiometabolic derangements in PCOS. Different PCOS phenotypes differ significantly in their cardiometabolic risk, which worsens with severity of androgen excess. Due to methodological difficulties, longer time-scale data about cardiovascular morbidity and mortality in PCOS and about possible beneficial effects of different treatment interventions is missing leaving many issues regarding cardiovascular risk unresolved.

Open access

Xiuzhen Zhang, Dan Xu, Ping Xu, Shufen Yang, Qingmei Zhang, Yan Wu, and Fengyi Yuan

Introduction

Metformin has been demonstrated to enhance cardioprotective benefits in type 1 diabetes (T1DM). Although glycemic variability (GV) is associated with increased risk of CVD in diabetes, there is a scarcity of research evaluating the effect of metformin on GV in T1DM.

Objectives

In the present study, the effects of adjuvant metformin therapy on GV and metabolic control in T1DM were explored.

Patients and methods

A total of 65 adults with T1DM were enrolled and subjected to physical examination, fasting laboratory tests, and continuous glucose monitoring, and subsequently randomized 1:1 to 3 months of 1000–2000 mg metformin daily add-on insulin (MET group, n = 34) or insulin (non-MET group, n = 31). After, baseline measurements were repeated.

Results

The mean amplitude of glycemic excursions was substantially reduced in MET group, compared with non-MET group (–1.58 (–3.35, 0.31) mmol/L vs 1.36 (–1.12, 2.24) mmol/L, P = 0.004). In parallel, the largest amplitude of glycemic excursions (–2.83 (–5.47, –0.06) mmol/L vs 0.45 (–1.29, 4.48) mmol/L, P = 0.004), the s.d. of blood glucose (–0.85 (–1.51, 0.01) mmol/L vs –0.14 (–0.68, 1.21) mmol/L, P = 0.015), and the coefficient of variation (–6.66 (–15.00, 1.50)% vs –1.60 (–6.28, 11.71)%, P = 0.012) all demonstrated improvement in the MET group, compared with the non-MET group. Significant reduction in insulin dose, BMI, and body weight was observed in patients in MET, not those in non-MET group.

Conclusion

Additional metformin therapy improved GV in adults with T1DM, as well as improving body composition and reducing insulin requirement. Hence, metformin as an adjunctive therapy has potential prospects in reducing the CVD risk in patients with T1DM in the long term.

Open access

Pinaki Dutta, Bhuvanesh Mahendran, K Shrinivas Reddy, Jasmina Ahluwalia, Kim Vaiphei, Rakesh K Kochhar, Prakamya Gupta, Anand Srinivasan, Mahesh Prakash, Kanchan Kumar Mukherjee, Viral N Shah, Girish Parthan, and Anil Bhansali

The effectiveness and short-term safety of recombinant human GH (r-hGH) in acromegaly patients with GH deficiency (GHD) after treatment are not well established. The study includes ten subjects with acromegaly who had GHD treated with r-hGH for 6 months. Control groups consisted of ten age-, gender-, and BMI-matched healthy subjects and ten active acromegaly patients who were treatment naïve. Body composition, quality of life (QoL), muscle strength, lipid profile, and cardiovascular risk factors were assessed in all subjects at baseline, and the same parameters were reassessed after 6 months of therapy with r-hGH in acromegaly with GHD. Repeat magnetic resonance imaging of the sella was performed in treated subjects. Optical colonoscopy was done and biopsies were taken from multiple sites for proliferation indices (Ki67). The median duration of GHD was 17.8 months and dose of r-hGH administered was 5.7±1.5 μg/kg per day. There was improvement in bone mineral content (P=0.01), bone mineral density (P=0.04), muscle strength (P<0.001), total cholesterol (P=0.003), high-density cholesterol (P<0.001), and QoL – score (P=0.005), and reduction in low-density cholesterol (P=0.003) and triglyceride (P=0.004) after treatment. There was no change in lean body mass, total body fat, hsCRP, lipoprotein (a), and fibrinogen levels. There was a modest increase in plasminogen activator inhibitor 1 (P=0.002), but it was lower compared with healthy controls and treatment naïve acromegalics (P=0.007). Six month-r-hGH therapy improves body composition, atherogenic lipid profile, QoL, and muscle strength in GHD patients who had acromegaly. Long-term prospective studies are needed to evaluate the effect of r-hGH therapy in these patients.

Open access

Nicolás Crisosto, Bárbara Echiburú, Manuel Maliqueo, Marta Luchsinger, Pedro Rojas, Sergio Recabarren, and Teresa Sir-Petermann

Context

Intrauterine life may be implicated in the origin of polycystic ovary syndrome (PCOS) modifying the endocrine and metabolic functions of children born to PCOS mothers independently of the genetic inheritance and gender. The aim of the present study was to evaluate the reproductive and metabolic functions in sons of women with PCOS during puberty.

Methods

Sixty-nine PCOS sons (PCOSs) and 84 control sons of 7–18 years old matched by the Tanner stage score were studied. A complete physical examination was conducted including anthropometric measurements (weight, height, waist, hip and body mass index). An oral glucose tolerance test was performed and circulating concentrations of luteinizing hormone, follicle-stimulating hormone (FSH), sex hormone-binding globulin, testosterone, androstenedione (A4), 17α-hydroxyprogesterone (17-OHP) and AMH were determined in the fasting sample.

Results

Waist-to-hip ratio, FSH and androstenedione levels were significantly higher in the PCOSs group compared to control boys during the Tanner stage II–III. In Tanner stages II–III and IV–V, PCOSs showed significantly higher total cholesterol and LDL levels. Propensity score analysis showed that higher LDL levels were attributable to the PCOSs condition and not to other metabolic factors. AMH levels were comparable during all stages. The rest of the parameters were comparable between both groups.

Conclusions

Sons of women with PCOS show increased total cholesterol and LDL levels during puberty, which may represent latent insulin resistance. Thus, this is a group that should be followed and studied looking for further features of insulin resistance and cardiovascular risk markers. Reproductive markers, on the other hand, are very similar to controls.

Open access

M von Wolff, C T Nakas, M Tobler, T M Merz, M P Hilty, J D Veldhuis, A R Huber, and J Pichler Hefti

Humans cannot live at very high altitude for reasons, which are not completely understood. Since these reasons are not restricted to cardiorespiratory changes alone, changes in the endocrine system might also be involved. Therefore, hormonal changes during prolonged hypobaric hypoxia were comprehensively assessed to determine effects of altitude and hypoxia on stress, thyroid and gonadal hypothalamus–pituitary hormone axes. Twenty-one male and 19 female participants were examined repetitively during a high-altitude expedition. Cortisol, prolactin, thyroid-stimulating hormone (TSH), fT4 and fT3 and in males follicle-stimulating hormone (FSH), luteinizing hormone (LH) and total testosterone were analysed as well as parameters of hypoxemia, such as SaO2 and paO2 at 550 m (baseline) (n = 40), during ascent at 4844 m (n = 38), 6022 m (n = 31) and 7050 m (n = 13), at 4844 m (n = 29) after acclimatization and after the expedition (n = 38). Correlation analysis of hormone concentrations with oxygen parameters and with altitude revealed statistical association in most cases only with altitude. Adrenal, thyroid and gonadal axes were affected by increasing altitude. Adrenal axis and prolactin were first supressed at 4844 m and then activated with increasing altitude; thyroid and gonadal axes were directly activated or suppressed respectively with increasing altitude. Acclimatisation at 4844 m led to normalization of adrenal and gonadal but not of thyroid axes. In conclusion, acclimatization partly leads to a normalization of the adrenal, thyroid and gonadal axes at around 5000 m. However, at higher altitude, endocrine dysregulation is pronounced and might contribute to the physical degradation found at high altitude.

Open access

Ananda A Santana-Ribeiro, Giulliani A Moreira-Brasileiro, Manuel H Aguiar-Oliveira, Roberto Salvatori, Vitor O Carvalho, Claudia K Alvim-Pereira, Carlos R Araújo-Daniel, Júlia G Reis-Costa, Alana L Andrade-Guimarães, Alécia A Oliveira-Santos, Edgar R Vieira, and Miburge B Gois-Junior

Objectives

Walking and postural balance are extremely important to obtain food and to work. Both are critical for quality of life and ability to survive. While walking reflects musculoskeletal and cardiopulmonary systems, postural balance depends on body size, muscle tone, visual, vestibular and nervous systems. Since GH and IGF-I act on all these systems, we decided to study those parameters in a cohort of individuals with severe short stature due to untreated isolated GH deficiency (IGHD) caused by a mutation in the GHRH receptor gene. These IGHD subjects, despite reduction in muscle mass, are very active and have normal longevity.

Methods

In a cross-sectional study, we assessed walking (by a 6-min walk test), postural balance (by force platform) and fall risk (by the 'Timed Up and Go' test) in 31 IGHD and 40 matched health controls.

Results

The percentage of the walked distance measured in relation to the predicted one was similar in groups, but higher in IGHD, when corrected by the leg length. Absolute postural balance data showed similar velocity of unipodal support in the two groups, and better values, with open and closed eyes and unipodal support, in IGHD, but these differences became non-significant when corrected for height and lower-limb length. The time in 'Timed Up and Go' test was higher in IGHD cohort, but still below the cut-off value for fall risk.

Conclusion

IGHD subjects exhibit satisfactory walking and postural balance, without increase in fall risk.

Open access

Marcus Quinkler, Bertil Ekman, Claudio Marelli, Sharif Uddin, Pierre Zelissen, Robert D Murray, and on behalf of the EU-AIR Investigators

Objective

Prednisolone is used as glucocorticoid replacement therapy for adrenal insufficiency (AI). Recent data indicate that its use in AI is associated with low bone mineral density. Data on risk factors for cardiovascular disease in patients with AI treated with prednisolone are scarce, despite this condition being the predominant cause of excess mortality. We aimed to address this question using real-world data from the European Adrenal Insufficiency Registry (EU-AIR).

Design/methods

EU-AIR, comprising of 19 centres across Germany, the Netherlands, Sweden and the UK, commenced enrolling patients with AI in August 2012. Patients receiving prednisolone (3–6 mg/day, n = 50) or hydrocortisone (15–30 mg/day, n = 909) were identified and grouped at a ratio of 1:3 (prednisolone:hydrocortisone) by matching for gender, age, duration and type of disease. Data from baseline and follow-up visits were analysed. Data from patients with congenital adrenal hyperplasia were excluded.

Results

Significantly higher mean ± s.d. total (6.3 ± 1.6 vs 5.4 ± 1.1 mmol/L; P = 0.003) and low-density lipoprotein (LDL) cholesterol levels (3.9 ± 1.4 vs 3.2 ± 1.0 mmol/L; P = 0.013) were identified in 47 patients on prednisolone vs 141 receiving hydrocortisone at baseline and at follow-up (P = 0.005 and P = 0.006, respectively). HbA1c, high-density lipoprotein and triglyceride levels, body mass index, systolic and diastolic blood pressure and waist circumference were not significantly different.

Conclusions

This is the first matched analysis of its kind. Significantly higher LDL levels in patients receiving prednisolone relative to hydrocortisone could predict a higher relative risk of cardiovascular disease in the former group.