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Sarantis Livadas Endocrine Unit, Athens Medical Centre, Athens, Greece

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Christina Bothou Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital of Zurich, Zurich, Switzerland

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Justyna Kuliczkowska-Płaksej Department of Endocrinology, Diabetology and Isotope Therapy, University of Medicine, Wrocław, Poland

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Ralitsa Robeva Ushate ‘acad. IV. Penchev’, Department of Endocrinology, Faculty of Medicine, Medical University-Sofia, Sofia, Bulgaria

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Andromahi Vryonidou Department of Endocrinology and Diabetes, Hellenic Red Cross Hospital, Athens, Greece

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Jelica Bjekic Macut Department of Endocrinology, UMC Bežanijska Kosa, Faculty of Medicine, University of Belgrade, Belgrade, Serbia

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Ioannis Androulakis Endocrine Unit, Athens Medical Centre, Athens, Greece

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Milica Opalic Clinic of Endocrinology, Diabetes and Metabolic Diseases, Faculty of Medicine, University of Belgrade, Belgrade, Serbia

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Zadalla Mouslech 1st Medical Propedeutic, Department of Internal Medicine, AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece

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Andrej Milewicz Department of Endocrinology, Diabetology and Isotope Therapy, University of Medicine, Wrocław, Poland

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Alessandra Gambineri Department of Medical and Surgical Science-DIMEC Endocrinology Unit, University of Bologna – S. Orsola-Mapighi Hospital, Italy

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Dimitrios Panidis Gynaecological Endocrinology Infirmary of the Second Department of Obstetrics and Gynaecology, Aristotle University of Thessaloniki, Thessaloniki, Greece

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Djuro Macut Clinic of Endocrinology, Diabetes and Metabolic Diseases, Faculty of Medicine, University of Belgrade, Belgrade, Serbia

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Background

Polycystic ovary syndrome (PCOS) is considered a risk factor for the development of type 2 diabetes mellitus (T2DM). However, which is the most appropriate way to evaluate dysglycemia in women with PCOS and who are at increased risk are as yet unclear.

Aim of the study

To determine the prevalence of T2DM, impaired glucose tolerance (IGT), and impaired fasting glucose (IFG) in PCOS women and potential factors to identify those at risk.

Subjects and methods

The oral glucose tolerance test (OGTT), biochemical/hormonal profile, and ovarian ultrasound data from 1614 Caucasian women with PCOS and 362 controls were analyzed in this cross-sectional multicenter study. The data were categorized according to age and BMI.

Results

Dysglycemia (T2DM, IGT, and IFG according to World Health Organization criteria) was more frequent in the PCOS group compared to controls: 2.2% vs 0.8%, P = 0.04; 9.5% vs 7.4%, P = 0.038; 14.2% vs 9.1%, P = 0.002, respectively. OGTT was essential for T2DM diagnosis, since in 88% of them basal glucose values were inconclusive for diagnosis. The presence of either T2DM or IFG was irrespective of age (P = 0.54) and BMI (P = 0.32), although the latter was associated with IGT (P = 0.021). There was no impact of age and BMI status on the prevalence of T2DM or IFG. Regression analysis revealed a role for age, BMI, fat deposition, androgens, and insulin resistance for dysglycemia. However, none of the factors prevailed as a useful marker employed in clinical practice.

Conclusions

One-third of our cohort of PCOS women with either T2DM or IGT displayed normal fasting glucose values but without confirming any specific predictor for dysglycemic condition. Hence, the evaluation of glycemic status using OGTT in all women with PCOS is strongly supported.

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Hui-qing Yuan Department of Endocrinology, Affiliated Hospital 2 of Nantong University, and First People’s Hospital of Nantong City, Nantong, China

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Jia-xi Miao Department of Endocrinology, Affiliated Hospital 2 of Nantong University, and First People’s Hospital of Nantong City, Nantong, China

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Jia-ping Xu Department of Endocrinology, Affiliated Hospital 2 of Nantong University, and First People’s Hospital of Nantong City, Nantong, China

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Su-xiang Zhu Department of Endocrinology, Affiliated Hospital 2 of Nantong University, and First People’s Hospital of Nantong City, Nantong, China

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Feng Xu Department of Endocrinology, Affiliated Hospital 2 of Nantong University, and First People’s Hospital of Nantong City, Nantong, China

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Xiao-hua Wang Department of Endocrinology, Affiliated Hospital 2 of Nantong University, and First People’s Hospital of Nantong City, Nantong, China

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Chun-hua Wang Department of Endocrinology, Affiliated Hospital 2 of Nantong University, and First People’s Hospital of Nantong City, Nantong, China

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Chao Yu Department of Clinical Laboratory, Affiliated Hospital 2 of Nantong University, and First People’s Hospital of Nantong City, Nantong, China

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Xue-qin Wang Department of Endocrinology, Affiliated Hospital 2 of Nantong University, and First People’s Hospital of Nantong City, Nantong, China

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Jian-bin Su Department of Endocrinology, Affiliated Hospital 2 of Nantong University, and First People’s Hospital of Nantong City, Nantong, China

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Dong-mei Zhang Medical Research Center, Affiliated Hospital 2 of Nantong University, and First People’s Hospital of Nantong City, Nantong, China

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Background

Increased serum cystatin C (CysC) can predict the onset of type 2 diabetes (T2D). Meanwhile, impaired pancreatic α- and β-cell functions get involved in the pathophysiological processes of T2D. So this study was to explore the relationships between serum CysC levels and pancreatic α- and β-cell functions in T2D.

Methods

In this cross-sectional observational study, a total of 2634 patients with T2D were consecutively recruited. Each recruited patient received a serum CysC test and oral glucose tolerance test for synchronous detection of serum C-peptide and plasma glucagon. As components of pancreatic β-cell function, insulin secretion and sensitivity indices were evaluated by C-peptide area under the curve (AUC-CP) and C-peptide-substituted Matsuda’s index (Matsuda-CP), respectively. Fasting glucagon (F-GLA) and post-challenge glucagon calculated by glucagon area under the curve (AUC-GLA) were used to assess pancreatic α-cell function. These skewed indices and were further natural log-transformed (ln).

Results

With quartiles of serum CysC levels ascending, AUC-CP, F-GLA and AUC-GLA were increased, while Matsuda-CP was decreased (P for trend <0.001). Moreover, serum CysC levels were positively related to lnAUC-CP, lnF-GLA and lnAUC-GLA (r= 0.241, 0.131 and 0.208, respectively, P < 0.001), and inversely related to lnMatsuda-CP (r= –0.195, P  < 0.001). Furthermore, after controlling for other relevant variables via multivariable linear regression analysis, serum CysC levels were identified to account for lnAUC-CP (β= 0.178, t= 10.518, P  < 0.001), lnMatsuda-CP (β= –0.137, t= –7.118, P  < 0.001), lnF-GLA (β= 0.049, t= 2.263, P = 0.024) and lnAUC-GLA (β= 0.121, t= 5.730, P  < 0.001).

Conclusions

Increased serum CysC levels may be partly responsible for increased insulin secretion from β-cells, decreased systemic insulin sensitivity, and elevated fasting and postprandial glucagon secretion from α-cells in T2D.

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Henry Zelada Division of Endocrinology, Diabetes and Metabolism, University of Alabama at Birmingham Heersink School of Medicine, Birmingham, Alabama, USA

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M Citlalli Perez-Guzman Internal Medicine Division of Endocrinology, Centro Médico ABC, Mexico City, Mexico

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Daniel R Chernavvsky Center for Diabetes Technology, University of Virginia, Charlottesville, Virginia, USA

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Rodolfo J Galindo Division of Endocrinology, Diabetes and Metabolism, University of Miami Miller School of Medicine. Miami, Florida, USA

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Over the last few years, several exciting changes in continuous glucose monitoring (CGM) technology have expanded its use and made CGM the standard of care for patients with type 1 and type 2 diabetes using insulin therapy. Consequently, hospitals started to notice increased use of these devices in their hospitalized patients. Furthermore during the coronavirus disease 2019 (COVID) pandemic, there was a critical need for innovative approaches to glycemic monitoring, and several hospitals started to implement CGM protocols in their daily practice. Subsequently, a plethora of studies have demonstrated the efficacy and safety of CGM use in the hospital, leading to clinical practice guideline recommendations. Several studies have also suggested that CGM has the potential to become the standard of care for some hospitalized patients, overcoming the limitations of current capillary glucose testing. Albeit, there is a need for more studies and particularly regulatory approval. In this review, we provide a historical overview of the evolution of glycemic monitoring in the hospital and review the current evidence, implementation protocols, and guidance for the use of CGM in hospitalized patients.

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Ann-Cathrin Koschker Division of Endocrinology and Diabetology, Department of Internal Medicine I, University Hospital, University of Würzburg, Würzburg, Germany
Comprehensive Heart Failure Center, University & University Hospital Würzburg, Würzburg, Germany

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Bodo Warrings Comprehensive Heart Failure Center, University & University Hospital Würzburg, Würzburg, Germany
Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital, University of Würzburg, Würzburg, Germany

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Caroline Morbach Comprehensive Heart Failure Center, University & University Hospital Würzburg, Würzburg, Germany
Division of Cardiology, Department of Internal Medicine I, University Hospital, University of Würzburg, Würzburg, Germany

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Florian Seyfried Department of General, Visceral, Transplant, Vascular, and Pediatric Surgery, University Hospital, University of Würzburg, Würzburg, Germany

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Nicole Rickert Department of Radiology, University Hospital, University of Würzburg, Würzburg, Germany

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Pius Jung Division of Pneumology, Department of Internal Medicine I, University Hospital, University of Würzburg, Würzburg, Germany

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Andreas Geier Division of Hepatology, Department of Internal Medicine II, University Hospital, University of Würzburg, Würzburg, Germany

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Ulrich Dischinger Division of Endocrinology and Diabetology, Department of Internal Medicine I, University Hospital, University of Würzburg, Würzburg, Germany

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Maike Krauthausen Department of General Practice, University Hospital, University of Würzburg, Würzburg, Germany

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Martin J Herrmann Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital, University of Würzburg, Würzburg, Germany

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Christine Stier Division of Endocrinology and Diabetology, Department of Internal Medicine I, University Hospital, University of Würzburg, Würzburg, Germany
Department of General, Visceral, Transplant, Vascular, and Pediatric Surgery, University Hospital, University of Würzburg, Würzburg, Germany

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Stefan Frantz Comprehensive Heart Failure Center, University & University Hospital Würzburg, Würzburg, Germany
Division of Cardiology, Department of Internal Medicine I, University Hospital, University of Würzburg, Würzburg, Germany

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Uwe Malzahn Center for Clinical Trials, University Hospital, University of Würzburg, Würzburg, Germany

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Stefan Störk Comprehensive Heart Failure Center, University & University Hospital Würzburg, Würzburg, Germany
Division of Cardiology, Department of Internal Medicine I, University Hospital, University of Würzburg, Würzburg, Germany

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Martin Fassnacht Division of Endocrinology and Diabetology, Department of Internal Medicine I, University Hospital, University of Würzburg, Würzburg, Germany
Comprehensive Heart Failure Center, University & University Hospital Würzburg, Würzburg, Germany

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the WAS Study Group
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the WAS Study Group

Obesity is a rapidly emerging health problem and an established risk factor for cardiovascular diseases. Bariatric surgery profoundly reduces body weight and mitigates sequelae of obesity. The open, randomized controlled Würzburg Adipositas Studie (WAS) trial compares the effects of Roux-en-Y gastric bypass (RYGB) vs psychotherapy-supported lifestyle modification in morbidly obese patients. The co-primary endpoint addresses 1-year changes in cardiovascular function (peak VO2 during cardiopulmonary exercise testing) and the quality of life (QoL) (Short-Form-36 physical functioning scale). Prior to randomization, all included patients underwent a multimodal anti-obesity treatment for 6–12 months. Thereafter, the patients were randomized and followed through month 12 to collect the primary endpoints. Afterwards, patients in the lifestyle group could opt for surgery, and final visit was scheduled for all patients 24 months after randomization. Sample size calculation suggested to enroll 90 patients in order to arrive at minimally 22 patients per group evaluable for the primary endpoint. Secondary objectives were to quantify changes in body weight, left ventricular hypertrophy, systolic and diastolic function (by echocardiography and cardiac MRI), functional brain MRI, psychometric scales, and endothelial and metabolic function. WAS enrolled 93 patients (72 women, median age 38 years, BMI 47.5 kg/m2) exhibiting a relevantly compromised exercise capacity (median peakVO2 18.3 mL/min/kg) and the QoL (median physical functioning scale 50). WAS is the first randomized controlled trial focusing on the effects of RYGB on cardiovascular function beyond hypertension. In addition, it will provide a wealth of high-quality data on the cerebral, psychiatric, hepatic, and metabolic function in obese patients after RYGB.

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Michelle J Galvan Metabolic, Nutrition, and Exercise Research (MiNER) Laboratory, Department of Kinesiology, University of Texas at El Paso, El Paso, Texas, USA

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Michael J Sanchez Metabolic, Nutrition, and Exercise Research (MiNER) Laboratory, Department of Kinesiology, University of Texas at El Paso, El Paso, Texas, USA

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Andrew J McAinch Institute for Health and Sport (IHES), Victoria University, Melbourne, Victoria, Australia
Australian Institute for Musculoskeletal Science (AIMSS), Victoria University, Melbourne, Victoria, Australia

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Jeffrey D Covington Department of Pathology, University of Massachusetts Medical School, Worcester, Massachusetts, USA

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Jason B Boyle Metabolic, Nutrition, and Exercise Research (MiNER) Laboratory, Department of Kinesiology, University of Texas at El Paso, El Paso, Texas, USA

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Sudip Bajpeyi Metabolic, Nutrition, and Exercise Research (MiNER) Laboratory, Department of Kinesiology, University of Texas at El Paso, El Paso, Texas, USA

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Introduction/purpose

Most US adults (54%) do not meet the minimum exercise recommendations by the American College of Sports Medicine. Neuromuscular electrical stimulation (NMES) is a novel alternate strategy to induce muscle contraction. However, the effectiveness of NMES to improve insulin sensitivity and energy expenditure is unclear. The purpose of this study was to investigate the effects of 4 weeks of NMES on glucose tolerance in a sedentary overweight or obese population.

Methods

Participants (n  = 10; age: 36.8 ± 3.8 years; BMI = 32 ± 1.3 kg/m2) were randomized into either control or NMES group. All participants received bilateral quadriceps stimulation (12 sessions; 30 min/session; three times/week at 50 Hz and 300 µs pulse width) altering pulse amplitude to either provide low-intensity sensory level (control; tingling sensation) or at high-intensity neuromuscular level (NMES; maximum tolerable levels with visible muscle contraction). Glucose tolerance was assessed by a 3-h oral glucose tolerance test (OGTT), and substrate utilization was measured by indirect calorimetry and body composition via dual X-ray absorptiometry at baseline and after 4 weeks of NMES intervention.

Results

Control and NMES groups had comparable fasting blood glucose, glucose tolerance, substrate utilization, and muscle mass at baseline. Four weeks of NMES resulted in a significant improvement in glucose tolerance measured by OGTT, whereas no change was observed in the control group. There was no change in substrate utilization and muscle mass in both control and NMES groups.

Conclusion

NMES is a novel and effective strategy to improve glucose tolerance in an at-risk overweight or obese sedentary population.

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Wang-shu Liu Department of Endocrinology, Affiliated Hospital 2 of Nantong University and First People’s Hospital of Nantong City, Nantong, China

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Ling-yan Hua Department of Ophthalmology, Affiliated Hospital 2 of Nantong University and First People’s Hospital of Nantong City, Nantong, China

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Su-xiang Zhu Department of Endocrinology, Affiliated Hospital 2 of Nantong University and First People’s Hospital of Nantong City, Nantong, China

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Feng Xu Department of Endocrinology, Affiliated Hospital 2 of Nantong University and First People’s Hospital of Nantong City, Nantong, China

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Xue-qin Wang Department of Endocrinology, Affiliated Hospital 2 of Nantong University and First People’s Hospital of Nantong City, Nantong, China

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Chun-feng Lu Department of Endocrinology, Affiliated Hospital 2 of Nantong University and First People’s Hospital of Nantong City, Nantong, China

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Jian-bin Su Department of Endocrinology, Affiliated Hospital 2 of Nantong University and First People’s Hospital of Nantong City, Nantong, China

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Feng Qi Emergency Intensive Care Unit, Affiliated Hospital 2 of Nantong University and First People’s Hospital of Nantong City, Nantong, China

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Background

The aim of the study was to explore whether plasma stromal cell-derived factor 1 (SDF-1) levels are associated with the EZSCAN score and its derived indicators in patients with type 2 diabetes (T2D).

Methods

From July 2020 to December 2020, a total of 253 patients with T2D were consecutively recruited. Serum SDF-1 levels were measured by sandwich ELISA. EZSCAN test was applied to evaluate the sudomotor function of each patient, and based on the results, EZSCAN score, cardiac autonomic neuropathy risk score (CANRS) and cardiovascular risk score (CVDRS) were calculated by particular algorithms. In addition, other relevant clinical data were also collected.

Results

With increasing tertiles of serum SDF-1 levels, the CANRS and CVDRS significantly increased (both Pfor trend <0.001), while the EZSCAN score significantly decreased (Pfor trend <0.001). Moreover, serum SDF-1 levels were significantly and positively correlated with the CANRS and CVDRS (r = 0.496 and 0.510, respectively, both P  < 0.001), and negatively correlated with the EZSCAN score (r = −0.391, P  < 0.001). Furthermore, multivariate linear regression analyses were constructed, and after adjusting for other clinical covariates, serum SDF-1 levels were independently responsible for EZSCAN score (β = −0.273, t = −3.679, P  < 0.001), CANRS (β = 0.334, t = 5.110, P  < 0.001) and CVDRS (β = 0.191, t = 4.983, P  = 0.003).

Conclusions

SDF-1 levels in serum were independently associated with the EZSCAN score and its derived indicators, such as CANRS and CVDRS in patients with T2D.

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Vânia Benido Silva Department of Endocrinology, Centro Hospitalar Universitário do Porto, Porto, Portugal

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Liliana Fonseca Department of Endocrinology, Centro Hospitalar Universitário do Porto, Porto, Portugal

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Maria Teresa Pereira Department of Endocrinology, Centro Hospitalar Universitário do Porto, Porto, Portugal

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Joana Vilaverde Department of Endocrinology, Centro Hospitalar Universitário do Porto, Porto, Portugal

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Clara Pinto Department of Obstetrics, Centro Hospitalar Universitário do Porto, Porto, Portugal

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Fernando Pichel Department of Nutrition, Centro Hospitalar Universitário do Porto, Porto, Portugal

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Maria do Céu Almeida In representation of the Diabetes and Pregnancy Study Group of the Portuguese Society of Diabetology, Lisbon, Portugal

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Jorge Dores Department of Endocrinology, Centro Hospitalar Universitário do Porto, Porto, Portugal

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Objective

Metformin has emerged as a safe and effective pharmacological alternative to insulin in gestational diabetes mellitus (GDM), being associated with lower maternal weight gain and hypoglycemia risk. Nevertheless, glycemic control is unaccomplished in a considerable proportion of women only treated with metformin. We aim to determine the metformin monotherapy failure rate in GDM and to identify predictors of its occurrence.

Design and methods

This was a retrospective multicenter study including pregnant women with GDM patients who started metformin as a first-line pharmacological treatment (n  = 2891). A comparative analysis of clinical and analytical data between the group of women treated with metformin monotherapy and those needing combined therapy with insulin was performed.

Results

In 685 (23.7%) women with GDM, combined therapy to achieve adequate glycemic control was required. Higher pregestational BMI (OR 1.039; CI 95% 1.008–1.071; P-value = 0.013), higher fasting plasma glucose (PG) levels in oral glucose tolerance test (OGTT) (OR 1.047; CI 95% 1.028–1.066; P-value <0.001) and an earlier gestational age (GA) at metformin introduction (0.839; CI 95% 0.796–0.885, P-value < 0.001) were independent predictive factors for metformin monotherapy failure. The best predictive cutoff values were a fasting PG in OGTT ≥87 mg/dL and GA at metformin introduction ≤29 weeks.

Conclusions

In 685 (23.7%) women, combined therapy with insulin to reach glycemic control was required. Higher pre-gestational BMI, fasting PG levels in OGTT ≥87 mg/dL and introduction of metformin ≤29 weeks of GA were independent predictive factors for metformin monotherapy failure. The early recognition of these characteristics can contribute to the establishment of individualized therapeutic strategies and attain better metabolic control during pregnancy.

Open access
Fabyan Esberard de Lima Beltrão Lauro Wanderley University Hospital, Federal University of Paraíba, João Pessoa, Paraíba, Brazil
Postgraduate Program in Nutritional Sciences, Department of Nutrition, Center for Health Sciences, Federal University of Paraíba, João Pessoa, Paraíba, Brazil
University Centre of João Pessoa (UNIPE), João Pessoa, Paraíba, Brazil

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Daniele Carvalhal de Almeida Beltrão University Centre of João Pessoa (UNIPE), João Pessoa, Paraíba, Brazil
Postgraduate Program in Cognitive Neuroscience and Behavior, Center for Health Sciences, Federal University of Paraíba, João Pessoa, Paraíba, Brazil

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Giulia Carvalhal Center for Biological and Health Sciences, Federal University of Campina Grande, Campina Grande, Paraíba, Brazil

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Fabyo Napoleão de Lima Beltrão Department of Medicine, Faculty of Medical Sciences, João Pessoa, Brazil

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Igor Motta de Aquino Metropolitan Hospital Dom José Maria Pires, Santa Rita, Paraíba, Brazil

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Thaíse da Silva Brito New Hope Medical School – FAMENE, João Pessoa, Paraíba, Brazil

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Barbara Costa Paulino Postgraduate Program in Nutritional Sciences, Department of Nutrition, Center for Health Sciences, Federal University of Paraíba, João Pessoa, Paraíba, Brazil

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Elisa Aires Postgraduate Program in Interactive Processes of Organs and Systems, Health & Science Institute, Federal University of Bahia, Salvador, Bahia, Brazil

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Diana Viegas Internal Medicine Department, rede UniFTC, Salvador, Bahia, Brazil

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Fabio Hecht The Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil

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Bruno Halpern Weight Control Centre, Hospital 9 de Julho, São Paulo, São Paulo, Brazil

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Liana Clebia De Morais Pordeus Postgraduate Program in Cognitive Neuroscience and Behavior, Center for Health Sciences, Federal University of Paraíba, João Pessoa, Paraíba, Brazil

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Maria da Conceição Rodrigues Gonçalves Postgraduate Program in Nutritional Sciences, Department of Nutrition, Center for Health Sciences, Federal University of Paraíba, João Pessoa, Paraíba, Brazil

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Helton Estrela Ramos Postgraduate Program in Interactive Processes of Organs and Systems, Health & Science Institute, Federal University of Bahia, Salvador, Bahia, Brazil
Department of Biorregulation, Health Sciences Institute, Federal University of Bahia, Bahia, Brazil
Postgraduate Program in Medicine and Health, Medical School of Medicine, Federal University of Bahia, Salvador, Bahia, Brazil

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Introduction

The severity of coronavirus disease 2019 (COVID-19) has been positively correlated with several comorbidities. The primary outcome of the study was to assess the relationship between the mortality and severity of COVID-19 and obesity classes according to BMI, visceral adipose tissue (VAT) area, s.c. adipose tissue area, muscle area (MA), and leptin levels.

Methods

In this prospective cohort study, 200 patients hospitalized with moderate-to-severe COVID-19 underwent an unenhanced CT of the thorax and laboratory tests, and leptin levels between June and August 2020 were obtained.

Results

Our study included 200 patients (male 52%; mean age: 62 (49–74) years; obesity (BMI > 30): 51.5%)). Fifty-eight patients (23.5%) were admitted to the intensive care unit and 29 (14.5%) died. In multivariate logistic regression (corrected for leptin, sex, age, and serum biomarkers) and receiver operating characteristic curve analyses, high VAT > 150 cm2 (odds ratio (OR): 6.15; P < 0.002), MA < 92 cm2 (OR: 7.94; P < 0.005), and VAT/MA ratio > 2 (OR: 13.9; P < 0.0001) were independent risk factors for mortality. Indeed, the Kaplan–Meier curves showed that patients with MA < 92 cm2 and without obesity (BMI < 30) had a lower survival rate (hazard ratio between 3.89 and 9.66; P < 0.0006) than the other groups. Leptin levels were not related to mortality and severity.

Conclusion

This prospective study reports data on the largest number of hospitalized severe COVID-19 patients and pinpoints VAT area and MA calculated by CT as predictors of COVID-19 mortality.

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Xi Cao Beijing Diabetes Institute, Beijing Tongren Hospital, Capital Medical University, Beijing, China

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Ming Lu Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, China

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Rong-Rong Xie Beijing Diabetes Institute, Beijing Tongren Hospital, Capital Medical University, Beijing, China

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Li-Ni Song Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, China

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Wei-Li Yang Beijing Diabetes Institute, Beijing Tongren Hospital, Capital Medical University, Beijing, China

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Zhong Xin Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, China

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Guang-Ran Yang Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, China

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Jin-Kui Yang Beijing Diabetes Institute, Beijing Tongren Hospital, Capital Medical University, Beijing, China

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Aims

In this study, we determined the association between thyroid-stimulating hormone (TSH) and diabetic macular edema (DME) by assessing the prevalence and risk factors for DME in type 2 diabetes mellitus (T2DM) patients with different thyroid dysfunctions.

Methods

This was a retrospective cross-sectional study including 1003 euthyroid and 92 subclinical hypothyroidism (SCH) T2DM patients. DME status was detected by optical coherence tomography (OCT). The association between TSH and DME and the impact of TSH on DME were analyzed.

Results

The DME prevalence was 28.3% in the SCH patients and 14.0% in the euthyroid population. The serum FT4 (P = 0.001) and FT3 (P < 0.001) levels were significantly higher in the non-DME group than in the DME group, and the TSH level (P < 0.001) was significantly lower. Four subgroups (G1–G4) were divided by TSH level, and the chi-square test indicated that even in the normal range, the TSH level was positively related to DME prevalence (P = 0.001). Subgroup data indicated that the association between TSH and DME detected by OCT (P = 0.001) was stronger than the correlation between TSH and diabetic retinopathy detected by digital retinal photographs (P = 0.027). The logistic regression model confirmed that elevated TSH was an independent risk factor for DME. The odds ratio was 1.53 (P = 0.02).

Conclusions

A high TSH level was an independent risk factor for DME. More attention should be given to the TSH level in T2DM patients due to its relationship with diabetic complications.

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Xue-Lian Zhang Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, China

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Xinyi Zhao Department of Physiology, School of Medicine, Jinan University, Guangzhou, China

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Yong Wu Department of Physiology, School of Medicine, Jinan University, Guangzhou, China
Department of Biomedical Engineering, Faculty of Engineering, The Hong Kong Polytechnic University, Hong Kong, China

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Wen-qing Huang Department of Transfusion Medicine, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong, China

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Jun-jiang Chen Department of Physiology, School of Medicine, Jinan University, Guangzhou, China
Department of Biomedical Engineering, Faculty of Engineering, The Hong Kong Polytechnic University, Hong Kong, China

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Peijie Hu Department of Biomedical Engineering, Faculty of Engineering, The Hong Kong Polytechnic University, Hong Kong, China

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Wei Liu Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, China

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Yi-Wen Chen Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, China

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Jin Hao Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, China

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Rong-Rong Xie Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, China

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Hsiao Chang Chan Epithelial Cell Biology Research Center, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China

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Ye Chun Ruan Department of Biomedical Engineering, Faculty of Engineering, The Hong Kong Polytechnic University, Hong Kong, China

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Hui Chen Cell-Gene Therapy Translational Medicine Research Center, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China

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Jinghui Guo Department of Physiology, School of Medicine, Jinan University, Guangzhou, China

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Objective

The beneficial effect of angiotensin(1–7) (Ang(1–7)), via the activation of its receptor, MAS-1, has been noted in diabetes treatment; however, how Ang(1–7) or MAS-1 affects insulin secretion remains elusive and whether the endogenous level of Ang(1–7) or MAS-1 is altered in diabetic individuals remains unexplored. We recently identified an important role of cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-activated Cl channel, in the regulation of insulin secretion. Here, we tested the possible involvement of CFTR in mediating Ang(1–7)’s effect on insulin secretion and measured the level of Ang(1–7), MAS-1 as well as CFTR in the blood of individuals with or without type 2 diabetes.

Methods

Ang(1–7)/MAS-1/CFTR pathway was determined by specific inhibitors, gene manipulation, Western blotting as well as insulin ELISA in a pancreatic β-cell line, RINm5F. Human blood samples were collected from 333 individuals with (n  = 197) and without (n  = 136) type 2 diabetes. Ang(1–7), MAS-1 and CFTR levels in the human blood were determined by ELISA.

Results

In RINm5F cells, Ang(1–7) induced intracellular cAMP increase, cAMP-response element binding protein (CREB) activation, enhanced CFTR expression and potentiated glucose-stimulated insulin secretion, which were abolished by a selective CFTR inhibitor, RNAi-knockdown of CFTR, or inhibition of MAS-1. In human subjects, the blood levels of MAS-1 and CFTR, but not Ang(1–7), were significantly higher in individuals with type 2 diabetes as compared to those in non-diabetic healthy subjects. In addition, blood levels of MAS-1 and CFTR were in significant positive correlation in type-2 diabetic but not non-diabetic subjects.

Conclusion

These results suggested that MAS-1 and CFTR as key players in mediating Ang(1–7)-promoted insulin secretion in pancreatic β-cells; MAS-1 and CFTR are positively correlated and both upregulated in type 2 diabetes.

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