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Global Health Research Institute, School of Human Development and Health, University of Southampton, Southampton, UK
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Gluteofemoral fat correlates negatively with a number of cardiometabolic disease risk factors, but the mechanisms involved in these relationships are unknown. The aim of this study was to test the hypothesis that gluteofemoral fat attenuates the risk of cardiometabolic disease by increasing blood adiponectin levels. This was a cross-sectional study in which arm, leg, gluteofemoral, abdominal s.c. and visceral fat levels were measured by dual-energy X-ray absorptiometry in 648 African females. Fasting serum adiponectin, lipid, insulin and plasma glucose levels and blood pressure were measured. Relationships between variables were analysed using multivariable linear regression and structural equation modelling. Adiponectin correlated positively (β = 0.45, P < 0.0001) with gluteofemoral fat in a multivariable regression model that included age, height, and arm, s.c. and visceral fat levels. In further regression models, there was a negative correlation of gluteofemoral fat with fasting glucose (β = −0.28; P < 0.0001) and triglyceride levels (β = −0.29; P < 0.0001) and insulin resistance (HOMA; β = −0.26; P < 0.0001). Structural equation modelling demonstrated that adiponectin mediated 20.7% (P < 0.01) of the association of gluteofemoral fat with insulin resistance and 16.1% (P < 0.01) of the association with triglyceride levels but only 6.67% (P = 0.31) of the association with glucose levels. These results demonstrate that gluteofemoral and leg fat are positively associated with adiponectin levels and that the negative association of lower body fat with insulin resistance and triglyceride levels may partially be mediated by this adipokine. Further studies are required to determine other factors that mediate the effect of lower body fat on cardiometabolic disease risk factors.
Department of Endocrinology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
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We assessed the prevalence of two novel islet autoantibodies, those targeting ubiquitin-conjugating enzyme 2L3 (UBE2L3) and eukaryote translation elongation factor 1 α1 (eEF1A1), in type 1 diabetes mellitus (T1DM) to evaluate their utility in T1DM diagnosis with comparison to other islet autoantibodies. We also aimed to determine whether age and ethnicity impacted their diagnostic value. Electrochemiluminescence assay was used to detect UBE2L3-Ab and eEF1A1-Ab in 193 Chinese Han and 570 American Caucasian subjects with T1DM, and 282 Chinese Han and 199 American Caucasian controls. In Chinese and American cohorts, the UBE2L3-Ab cut-off indices were 0.039 and 0.038, and the eEF1A1-Ab cut-off indices were 0.048 and 0.050, respectively. The prevalence of UBE2L3-Ab was significantly higher in the Chinese (9.33%) and American (3.86%) subjects with T1DM than in the controls (P < 0.05). The prevalence of UBE2L3-Ab in T1DM was significantly higher in Chinese than in American (P < 0.05). Albeit not statistically significant, the prevalence of UBE2L3-Ab in T1DM was slightly higher in children than in adults of both ethnicities. The differences in eEF1A1-Ab levels between subjects with T1DM and controls were not significant. Meanwhile, all American subjects with UBE2L3-Ab also harbored glutamic acid decarboxylase autoantibody (GADA) or insulin autoantibody (IAA). In contrast, 2.07% of the Chinese subjects with UBE2L3-Ab positive were previously classified as autoantibody-negative based on GADA and IAA. So the prevalence of UBE2L3-Ab in T1DM patients was significantly higher than in controls and was variable according to ethnicity as well as tended to be higher in children than adults. However, UBE2L3-Ab and eEF1A1-Ab may not be reliable diagnostic biomarkers forT1DM.
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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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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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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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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.
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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Postgraduate Program in Cognitive Neuroscience and Behavior, Center for Health Sciences, Federal University of Paraíba, João Pessoa, Paraíba, Brazil
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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.
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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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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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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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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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.
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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Department of Pediatrics, University of Turku and Turku University Hospital, Turku, Finland
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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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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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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.
