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Zhiyan Yu Department of Endocrinology, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, China

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Yueyue Wu Department of Endocrinology, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, China

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Rui Zhang Department of Endocrinology, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, China

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Yue Li Department of Endocrinology, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, China

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Shufei Zang Department of Endocrinology, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, China

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Jun Liu Department of Endocrinology, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, China

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Background

This study aimed to investigate the association of non-alcoholic fatty liver disease (NAFLD) and liver fibrosis with osteoporosis in postmenopausal women and men over 50 years of age with type 2 diabetes (T2DM).

Methods

In this study, 1243 patients with T2DM (T2DM with coexistent NAFLD, n  = 760; T2DM with no NAFLD, n  = 483) were analysed. Non-invasive markers, NAFLD fibrosis score (NFS) and fibrosis index based on four factors (FIB-4), were applied to evaluate NAFLD fibrosis risk.

Results

There was no significant difference in bone mineral density (BMD) between the NAFLD group and the non-NAFLD group or between males and females after adjusting for age, BMI and gender. In postmenopausal women, there was an increased risk of osteoporosis (odds ratio (OR): 4.41, 95% CI: 1.04–18.70, P = 0.039) in the FIB-4 high risk group compared to the low risk group. Similarly, in women with high risk NFS, there was an increased risk of osteoporosis (OR: 5.98, 95% CI: 1.40–25.60, P = 0.043) compared to the low risk group. Among men over 50 years old, there was no significant difference in bone mineral density between the NAFLD group and the non-NAFLD group and no significant difference between bone mineral density and incidence of osteopenia or osteoporosis among those with different NAFLD fibrosis risk.

Conclusion

There was a significant association of high risk for NAFLD liver fibrosis with osteoporosis in postmenopausal diabetic women but not men. In clinical practice, gender-specific evaluation of osteoporosis is needed in patients with T2DM and coexistent NAFLD.

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Wei Liu Department of Endocrinology and Metabolism, Peking University People’s Hospital, Beijing, People’s Republic of China

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Yunke Ma Department of Endocrinology and Metabolism, Peking University People’s Hospital, Beijing, People’s Republic of China

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Xiaoling Cai Department of Endocrinology and Metabolism, Peking University People’s Hospital, Beijing, People’s Republic of China

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Yu Zhu Department of Endocrinology and Metabolism, Peking University People’s Hospital, Beijing, People’s Republic of China

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Mingxia Zhang Department of Endocrinology and Metabolism, Peking University People’s Hospital, Beijing, People’s Republic of China

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Juan Li Department of Endocrinology and Metabolism, Peking University People’s Hospital, Beijing, People’s Republic of China

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Jing Chen School of Automation, Beijing Institute of Technology, Beijing, People’s Republic of China

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Dawei Shi School of Automation, Beijing Institute of Technology, Beijing, People’s Republic of China

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Linong Ji Department of Endocrinology and Metabolism, Peking University People’s Hospital, Beijing, People’s Republic of China

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Objective

To explore the relationship between C-peptide secretion and time in range (TIR) in adult patients with type 1 diabetes.

Methods

From December 2018 to December 2020, 76 type 1 diabetes participants were enrolled from the Department of Endocrinology and Metabolism of Peking University People’s Hospital. All participants wore intermittently scanned continuous glucose monitoring (isCGM), and insulin dosage was adjusted according to standardized clinical procedures. Subjects were divided into low C-peptide group (<10 pmol/L) and preserved C-peptide group (10–200 pmol/L) based on fasting serum C-peptide levels. Differences of TIR, metrics related to glucose variability and hypoglycemic events were compared.

Results

A total of 94,846 isCGM values obtained from 39 male and 37 female participants were analyzed. Individuals with preserved C-peptide secretion had shorter diabetes duration (2.0 (0.5, 10.0) vs 10.0 (3.0, 18.3) years, P = 0.002). TIR was higher in the individuals with preserved C-peptide than those with decreased C-peptide (67.1% (54.2, 75.8) vs 45.5% (33.9, 56.1), P < 0.001), and time above range was significantly lower in those with preserved C-peptide (28.0% (15.6, 42.4) vs 49.4% (39.1, 64.2), P < 0.001). Preserved C-peptide was associated with lower glucose variability, as defined by s.d. (3.0 mmol/L (2.6, 3.4) vs 3.8 mmol/L (3.2, 4.3), P < 0.001) and interquartile range (4.3 mmol/L (3.1, 4.8) vs 5.3 mmol/L (4.5, 6.3), P < 0.001). Metrics related to hypoglycemia were not different between the two groups.

Conclusion

Preserved C-peptide secretion was associated with higher TIR and lower glucose variability in Chinese type 1 diabetes adults.

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Nobuo Matsuura Department of Pediatrics, Kitasato University School of Medicine, Sagamihara, Japan

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Tadashi Kaname Department of Genome Medicine, National Research Institute for Child Health and Development, Tokyo, Japan

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Norio Niikawa Health Sciences University of Hokkaido, Sapporo, Japan

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Yoshihide Ooyama Department of Pediatrics, Kitasato University School of Medicine, Sagamihara, Japan

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Osamu Shinohara Shinohara Child Clinic, Machida, Japan

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Yukifumi Yokota Department of Pediatrics, Kitasato University School of Medicine, Sagamihara, Japan

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Shigeyuki Ohtsu Department of Pediatrics, Kitasato University School of Medicine, Sagamihara, Japan

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Noriyuki Takubo Department of Pediatrics, Kitasato University School of Medicine, Sagamihara, Japan

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Kazuteru Kitsuda Department of Pediatrics, Kitasato University School of Medicine, Sagamihara, Japan

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Keiko Shibayama Department of Pediatrics, Kitasato University School of Medicine, Sagamihara, Japan

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Fumio Takada Department of Medical Genetics, Kitasato University Graduate School of Medical Science, Sagamihara, Japan

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Akemi Koike Miyanosawa Child Clinic, Sapporo, Japan

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Hitomi Sano Department of Pediatric, Sapporo City General Hospital, Sapporo, Japan

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Yoshiya Ito Department of Clinical Medicine, Japanese Red Cross Hospital Collage of Nursing, Kitami, Japan

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Kenji Ishikura Department of Pediatrics, Kitasato University School of Medicine, Sagamihara, Japan

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Objective

This study aimed to report on 15 Japanese patients with acrodysostosis and pseudohypoparathyroidism (PHP) and analyze them using the newly proposed classification of the EuroPHP network to determine whether this classification system is suitable for Japanese patients.

Design

We divided the patients into three groups based on hormone resistance, the number of fingers with short metacarpals, the existence of cone-shaped epiphyses and gene defects.

Methods

We carried out clinical, radiological and genetic evaluations of two patients in group A (iPPSD5), six patients in group B (iPPDS4) and seven patients in group C (iPPSD2).

Results

Group A consisted of two siblings without hormone resistance who had the most severe bone and physical developmental delays. PDE4D gene defects were detected in both cases. Group B consisted of six patients who showed hormone resistance without hypocalcemia. Short metacarpal bones with corn-shaped epiphyses were observed in all patients. In two cases, PRKAR1A gene defects were detected; however, their clinical and radiological features were not identical. The facial dysmorphism and developmental delay were less severe and PRKAR1A gene defects were detected in case B-3. Severe facial dysmorphism and deformity of metacarpal bones were observed, but no gene defect was detected in case B-1. Group C consisted of seven patients with PHP1a, four of whom had maternally inherited heterozygous inactivating mutations in one of the GNAS genes. The clinical and radiological features of the patients in group C were not identical either.

Conclusions

The newly proposed classification is suitable for Japanese patients; however, heterogeneities still existed within groups B and C.

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Aliyu Tijani Jibril Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran

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Ahmad Jayedi Social Determinants of Health Research Center, Semnan University of Medical Sciences, Semnan, Iran

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Sakineh Shab-Bidar Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran

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Objective

To examine the dose-dependent influence of oral alpha-lipoic acid (ALA) supplementation on cardiometabolic risk factors in patients with type 2 diabetes (T2D).

Design

We followed the instructions outlined in the Cochrane Handbook for Systematic Reviews of Interventions and the Grading of Recommendations, Assessment, Development, and Evaluation Handbook to conduct our systematic review. The protocol of the study was registered in PROSPERO (CRD42021260587).

Method

We searched PubMed, Scopus, and Web of Science to May 2021 for trials of oral ALA supplementation in adults with T2D. The primary outcomes were HbA1c, weight loss, and LDL cholesterol (LDL-C). Secondary outcomes included fasting plasma glucose (FPG), triglyceride (TG), C-reactive protein (CRP), and blood pressure. We conducted a random-effects dose–response meta-analysis to calculate the mean difference (MD) and 95% CI for each 500 mg/day oral ALA supplementation. We performed a nonlinear dose–response meta-analysis using a restricted cubic spline.

Results

We included 16 trials with 1035 patients. Each 500 mg/day increase in oral ALA supplementation significantly reduced HbA1c, body weight, CRP, FPG, and TG. Dose–response meta-analyses indicated a linear decrement in body weight at ALA supplementation of more than 600 mg/day (MD600 mg/day: −0.30 kg, 95% CI: −0.04, −0.57). A relatively J-shaped effect was seen for HbA1c (MD: −0.32%, 95% CI: −0.45, −0.18). Levels of FPG and LDL-C decreased up to 600 mg/day ALA intake. The point estimates were below minimal clinically important difference thresholds for all outcomes.

Conclusion

Despite significant improvements, the effects of oral ALA supplementation on cardiometabolic risk factors in patients with T2D were not clinically important.

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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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Ziting Liang Department of Respiratory, Shandong Provincial Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
Department of Respiratory, Shandong Provincial Qianfoshan Hospital, Shandong University, The First Affiliated Hospital of Shandong First Medical University, Shandong Institute of Respiratory Diseases, Jinan, China

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Mengge Yang Department of Respiratory, Shandong Provincial Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
Department of Respiratory, Shandong Provincial Qianfoshan Hospital, Shandong University, The First Affiliated Hospital of Shandong First Medical University, Shandong Institute of Respiratory Diseases, Jinan, China

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Changjuan Xu Department of Respiratory, Shandong Provincial Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
Department of Respiratory, Shandong Provincial Qianfoshan Hospital, Shandong University, The First Affiliated Hospital of Shandong First Medical University, Shandong Institute of Respiratory Diseases, Jinan, China

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Rong Zeng Department of Respiratory, Shandong Provincial Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
Department of Respiratory, Shandong Provincial Qianfoshan Hospital, Shandong University, The First Affiliated Hospital of Shandong First Medical University, Shandong Institute of Respiratory Diseases, Jinan, China

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Liang Dong Department of Respiratory, Shandong Provincial Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
Department of Respiratory, Shandong Provincial Qianfoshan Hospital, Shandong University, The First Affiliated Hospital of Shandong First Medical University, Shandong Institute of Respiratory Diseases, Jinan, China

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Aim

This study aimed to investigate the effects and safety of metformin in patients with concurrent diabetes mellitus (DM) and chronic obstructive pulmonary disease (COPD).

Methods

PubMed, Embase, Web of Science, the China National Knowledge, and Cochrane Database were searched to find studies that examined the effects and safety of metformin in patients with concurrent DM and COPD. We conducted a meta-analysis with a risk ratio (RR) and assessed the quality of included studies and pooled evidence.

Results

Eight studies were involved. Metformin was associated with lower risk of COPD-related hospitalizations (RR: 0.72, 95% CI: 0.53–0.98; I2= 89%) and all-cause mortality (RR: 0.60, 95% CI: 0.36–1.01, I2= 69%) in patients with concurrent DM and COPD, but did not increase the risk of hyperlactatemia (RR: 1.14, 95% CI: 0.92–1.41, I2 = 8%).

Conclusions

Metformin use is associated with lower risk of COPD-related hospitalizations and risk of all-cause mortality without increasing the risk of hyperlactatemia. Considerations should be given to conduct more high-quality randomized trials involving larger samples.

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Olli Helminen Department of Pediatrics, PEDEGO Research Group, Medical Research Center, Oulu University, Hospital and University of Oulu, Oulu, Finland
Surgery Research Unit, Cancer and Translational Medicine Research Unit, Medical Research Center Oulu, University of Oulu and Oulu University Hospital, Oulu, Finland

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Tytti Pokka Department of Pediatrics, PEDEGO Research Group, Medical Research Center, Oulu University, Hospital and University of Oulu, Oulu, Finland

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Susanna Aspholm Tampere Centre for Child Health Research, Tampere University Hospital, Tampere, Finland

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Jorma Ilonen Immunogenetics Laboratory, University of Turku, Turku, Finland
Department of Pediatrics, University of Turku and Turku University Hospital, Turku, Finland

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Olli G Simell Department of Pediatrics, University of Turku and Turku University Hospital, Turku, Finland

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Mikael Knip Tampere Centre for Child Health Research, Tampere University Hospital, Tampere, Finland
Pediatric Research Center, New Children’s Hospital, Helsinki University Hospital, Helsinki, Finland
Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland

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Riitta Veijola Department of Pediatrics, PEDEGO Research Group, Medical Research Center, Oulu University, Hospital and University of Oulu, Oulu, Finland

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Objective

Subtypes in type 1 diabetes pathogenesis have been implicated based on the first-appearing autoantibody (primary autoantibody). We set out to describe the glucose metabolism in preclinical diabetes in relation to the primary autoantibody in children with HLA-conferred disease susceptibility.

Design and methods

Dysglycemic markers are defined as a 10% increase in HbA1c in a 3–12 months interval or HbA1c ≥5.9% (41 mmol/mol) in two consecutive samples, impaired fasting glucose or impaired glucose tolerance, or a random plasma glucose value ≥7.8 mmol/L. A primary autoantibody could be detected in 295 children who later developed at least 1 additional biochemical autoantibody. These children were divided into three groups: insulin autoantibody (IAA) multiple (n  = 143), GAD antibody (GADA) multiple (n  = 126) and islet antigen 2 antibody (IA-2A) multiple (n  = 26). Another 229 children seroconverted to positivity only for a single biochemical autoantibody and were grouped as IAA only (n  = 87), GADA only (n  = 114) and IA-2A only (n  = 28).

Results

No consistent differences were observed in selected autoantibody groups during the preclinical period. At diagnosis, children with IAA only showed the highest HbA1c (P < 0.001 between groups) and the highest random plasma glucose (P = 0.005 between groups). Children with IA-2A only progressed to type 1 diabetes as frequently as those with IA-2A multiple (46% vs 54%, P = 0.297) whereas those with IAA only or GADA only progressed less often than children with IAA multiple or GADA multiple (22% vs 62% (P < 0.001) and 7% vs 43% (P < 0.001)), respectively.

Conclusions

The phenotype of preclinical diabetes defined by the primary autoantibody is not associated with any discernible differences in glucose metabolism before the clinical disease manifestation.

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Giovanni Fanni Department of Medical Sciences, Clinical Diabetes and Metabolism, Uppsala University, Uppsala, Sweden

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Petros Katsogiannos Department of Medical Sciences, Clinical Diabetes and Metabolism, Uppsala University, Uppsala, Sweden

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Bipasha Nandi Jui Department of Medical Sciences, Clinical Diabetes and Metabolism, Uppsala University, Uppsala, Sweden

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Magnus Sundbom Department of Surgical Sciences, Uppsala University, Uppsala, Sweden

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Susanne Hetty Department of Medical Sciences, Clinical Diabetes and Metabolism, Uppsala University, Uppsala, Sweden

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Maria J Pereira Department of Medical Sciences, Clinical Diabetes and Metabolism, Uppsala University, Uppsala, Sweden

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Jan W Eriksson Department of Medical Sciences, Clinical Diabetes and Metabolism, Uppsala University, Uppsala, Sweden

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Purpose

In patients with type 2 diabetes mellitus (T2DM), Roux-en-Y gastric bypass (RYGB) leads to beneficial metabolic adaptations, including enhanced incretin secretion, beta-cell function, and systemic insulin sensitivity. We explored the impact of RYGB on pituitary, pancreatic, gut hormones, and cortisol responses to parenteral and enteral nutrient stimulation in patients with obesity and T2DM with repeated sampling up to 2 years after intervention.

Methods

We performed exploratory post hoc analyses in a previously reported randomized trial. Levels of adrenocorticotropic hormone (ACTH), cortisol, growth hormone (GH), glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), peptide YY (PYY), ACTH, insulin, and glucagon were measured in 13 patients with T2DM and obesity at four different visits: before and 4, 24, and 104 weeks after RYGB; and in three sequential conditions on the same day: fasting, intravenous arginine challenge, and OGTT.

Results

RYGB surprisingly induced a rise in ACTH, cortisol, and GH levels upon an oral glucose load, together with enhanced GLP-1 and PYY responses. Fasting and post-arginine GH levels were higher after RYGB, whereas insulin, glucagon, GLP-1, GIP, and cortisol were lower. These endocrine adaptations were seen as early as 4 weeks after surgery and were maintained for up to 2 years.

Conclusion

These findings indicate adaptations of glucose sensing mechanisms and responses in multiple endocrine organs after RYGB, involving the gut, pancreatic islets, the pituitary gland, the adrenals, and the brain.

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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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Mohamed Asrih Service of Endocrinology, Diabetes, Nutrition and Patient Therapeutic Education, Geneva University Hospitals, Geneva, Switzerland

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Flore Sinturel Thoracic and Endocrine Surgery Division, Department of Surgery, Geneva University Hospitals (HUG), Geneva, Switzerland
Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland
Diabetes Center, Faculty of Medicine, University of Geneva, Geneva, Switzerland

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Richard Dubos Department and Division of Primary Care Medicine, Geneva University Hospitals (HUG), Geneva, Switzerland

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Idris Guessous Department and Division of Primary Care Medicine, Geneva University Hospitals (HUG), Geneva, Switzerland

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Zoltan Pataky Service of Endocrinology, Diabetes, Nutrition and Patient Therapeutic Education, Geneva University Hospitals, Geneva, Switzerland
Diabetes Center, Faculty of Medicine, University of Geneva, Geneva, Switzerland

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Charna Dibner Thoracic and Endocrine Surgery Division, Department of Surgery, Geneva University Hospitals (HUG), Geneva, Switzerland
Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland
Diabetes Center, Faculty of Medicine, University of Geneva, Geneva, Switzerland

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François R Jornayvaz Service of Endocrinology, Diabetes, Nutrition and Patient Therapeutic Education, Geneva University Hospitals, Geneva, Switzerland
Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland
Diabetes Center, Faculty of Medicine, University of Geneva, Geneva, Switzerland

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Karim Gariani Service of Endocrinology, Diabetes, Nutrition and Patient Therapeutic Education, Geneva University Hospitals, Geneva, Switzerland
Diabetes Center, Faculty of Medicine, University of Geneva, Geneva, Switzerland

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Objective

Growth differentiation factor-15 (GDF15), a key metabolic regulator, is associated with obesity and diabetes in which sex-specific differences have been reported. Thus, we assessed whether GDF15 could be dependent on sex in diabetes and/or obesity groups.

Methods

We measured serum GDF15 levels by ELISA in eight lean women and men (n = 16), eight women and eight men having obesity (n = 16), eight women and eight men with type 2 diabetes (T2D, n = 16), and seven women and nine men with both diabetes and obesity (n = 16). Estimation of the difference in the means of each group was performed by two-way ANOVA. The interdependence of the different variates was addressed by multivariate analysis. Correlations between GDF15 levels and HOMA-IR, HbA1c, triglycerides, HDL, and LDL were explored by linear regression.

Results

Being a woman and having obesity alone or in combination with diabetes decreased GDF15 serum levels (β = −0.47, CI = −0.95, 0.00, P = 0.052; β = −0.45, CI = −0.94, 0.05, P= 0.075). Diabetes independently of metformin treatment and obesity were not predictive of low GDF15 levels (β = 0.10, CI = −0.36, 0.57, P = 0.7). Correlation analysis showed that HOMA-IR (r = 0.45, P = 0.008) and triglycerides (r = 0.41, P = 0.017) were positively correlated and HDL (r = −0.48, P = 0.005) was negatively correlated with GDF15 levels in men.

Conclusions/interpretation

GDF15 level was significantly different between men and women, as well as between the groups. Sex and group interaction revealed that being a woman and having obesity alone or in combination with diabetes decreased GDF15 levels.

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