Sex differences in body composition in people with prediabetes and type 2 diabetes as compared with people with normal glucose metabolism: the Maastricht Study

Rianneke de Ritter1,2 ● Simone J. S. Sep1,2,3 & Marleen M. J. van Greevenbroek1,2 & Yvo H. A. M. Kusters1,2 & Rimke C. Vos4,5 ● Michiel L. Bots4 ● M. Eline Kooi2,6 ● Pieter C. Dagnelie1,2 ● Simone J. P. M. Eussen2,7,8 ● Miranda T. Schram1,2,9,10 ● Annemarie Koster8,11 ● Martijn C. G. Brouwers 1,2 ● Niels M. R. van der Sangen12 ● Sanne A. E. Peters4,13 ● Carla J. H. van der Kallen1,2 ● Coen D. A. Stehouwer1,2

Received: 27 May 2022 / Accepted: 22 November 2022 / Published online: 20 February 2023 © The Author(s) 2023

Abstract

Aims/hypothesis Obesity is a major risk factor for type 2 diabetes. However, body composition differs between women and men. In this study we investigate the association between diabetes status and body composition and whether this association is moderated by sex.

Methods In a population-based cohort study (n=7639; age 40–75 years, 50% women, 25% type 2 diabetes), we estimated the sex-specific associations, and differences therein, of prediabetes (i.e. impaired fasting glucose and/or impaired glucose tolerance) and type 2 diabetes (reference: normal glucose metabolism [NGM]) with dual-energy x-ray absorptiometry (DEXA)- and MRIderived measures of body composition and with hip circumference. Sex differences were analysed using adjusted regression models with interaction terms of sex-by-diabetes status.

Results Compared with their NGM counterparts, both women and men with prediabetes and type 2 diabetes had more fat and lean mass and a greater hip circumference. The differences in subcutaneous adipose tissue, hip circumference and total and peripheral lean mass between type 2 diabetes and NGM were greater in women than men (women minus men [W–M] mean difference [95% CI]: 15.0 cm2 [1.5, 28.5], 3.2 cm [2.2, 4.1], 690 g [8, 1372] and 443 g [142, 744], respectively). The difference in visceral adipose tissue between type 2 diabetes and NGM was greater in men than women (W–M mean difference [95% CI]: −14.8 cm2 [−26.4, −3.1]). There was no sex difference in the percentage of liver fat between type 2 diabetes and NGM. The differences in measures of body composition between prediabetes and NGM were generally in the same direction, but were not significantly different between women and men.

Conclusions/interpretation This study indicates that there are sex differences in body composition associated with type 2 diabetes. The pathophysiological significance of these sex-associated differences requires further study.

Rianneke de Ritter

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1 Department of Internal Medicine, Maastricht University Medical Center+, Maastricht, the Netherlands

2 CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, the Netherlands

3 Adelante, Center of Expertise in Rehabilitation and Audiology, Hoensbroek, the Netherlands

4 Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands

5 Leiden University Medical Center, Department of Public Health and Primary Care/LUMC-Campus, The Hague, the Netherlands

6 Department of Radiology and Nuclear Medicine, Maastricht University Medical Center+, Maastricht, the Netherlands

7 Department of Epidemiology, Maastricht University, Maastricht, the Netherlands

8 CAPHRI Care and Public Health Research Institute, Maastricht University, Maastricht, the Netherlands

9 Heart and Vascular Center, Maastricht University Medical Center+, Maastricht, the Netherlands

10 MHeNs School for Mental Health and Neuroscience, Maastricht University Medical Center+, Maastricht, the Netherlands

11 Department of Social Medicine, Maastricht University, Maastricht, the Netherlands

12 Department of Cardiology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands

13 The George Institute for Global Health, Imperial College London, London, UK

Keywords Body composition . DEXA . Fat mass . Lean mass . Liver fat . MRI . Prediabetes . Sex differences . Type 2 diabetes . Women

Abbreviations

DEXA Dual-energy x-ray absorptiometry

GMR Geometric mean ratio

GMS Glucose metabolism status

NGM Normal glucose metabolism

SAT Subcutaneous adipose tissue

VAT Visceral adipose tissue

W–M Women minus men

Long-term cost-effectiveness of implementing a lifestyle intervention during pregnancy to reduce the incidence of gestational diabetes and type 2 diabetes

Melanie Lloyd1,2 iD Jedidiah Morton1,2,3 ● Helena Teede2 ● Clara Marquina1 ● Dina Abushanab1 ● Dianna J. Magliano2,3 ● Emily J. Callander2 ● Zanfina Ademi1,2

Received: 25 August 2022 /Accepted: 31 January 2023 © The Author(s) 2023

Abstract

Aims/hypothesis The aim of this study was to determine the long-term cost-effectiveness and return on investment of implementing a structured lifestyle intervention to reduce excessive gestational weight gain and associated incidence of gestational diabetes mellitus (GDM) and type 2 diabetes mellitus.

Methods A decision-analytic Markov model was used to compare the health and cost-effectiveness outcomes for (1) a structured lifestyle intervention during pregnancy to prevent GDM and subsequent type 2 diabetes; and (2) current usual antenatal care. Life table modelling was used to capture type 2 diabetes morbidity, mortality and quality-adjusted life years over a lifetime horizon for all women giving birth in Australia. Costs incorporated both healthcare and societal perspectives. The intervention effect was derived from published meta-analyses. Deterministic and probabilistic sensitivity analyses were used to capture the impact of uncertainty in the model.

Results The model projected a 10% reduction in the number of women subsequently diagnosed with type 2 diabetes through implementation of the lifestyle intervention compared with current usual care. The total net incremental cost of intervention was approximately AU$70 million, and the cost savings from the reduction in costs of antenatal care for GDM, birth complications and type 2 diabetes management were approximately AU$85 million. The intervention was dominant (cost-saving) compared with usual care from a healthcare perspective, and returned AU$1.22 (95% CI 0.53, 2.13) per dollar invested. The results were robust to sensitivity analysis, and remained cost-saving or highly cost-effective in each of the scenarios explored.

Conclusions/interpretation This study demonstrates significant cost savings from implementation of a structured lifestyle intervention during pregnancy, due to a reduction in adverse health outcomes for women during both the perinatal period and over their lifetime.

Keywords Cost-effectiveness . Decision modelling . Dietary intervention . Epidemiology . Gestational diabetes mellitus . Life table modelling . Physical activity . Pregnancy . Type 2 diabetes mellitus

Zanfina Ademi

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1 Centre for Medicine Use and Safety, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Melbourne, Australia

2 School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia

3 Diabetes and Population Health, Baker Heart and Diabetes Institute, Melbourne, Australia

Islet Autoantibody Standardization Program: interlaboratory comparison of insulin autoantibody assay performance in 2018 and 2020 workshops

Ilaria Marzinotto1 iD David L. Pittman2 iD Alistair J. K. Williams3 iD Anna E. Long3 iD Peter Achenbach4 iD Michael Schlosser5,6 & Beena Akolkar7 iD William E. Winter2 & Vito Lampasona1 iD participating laboratories

Received: 30 August 2022 /Accepted: 21 December 2022 / The Author(s) 2023

Abstract

Aims/hypothesis The Islet Autoantibody Standardization Program (IASP) aims to improve the performance of immunoassays measuring autoantibodies in type 1 diabetes and the concordance of results across laboratories. IASP organises international workshops distributing anonymised serum samples to participating laboratories and centralises the collection and analysis of results. In this report, we describe the results of assays measuring IAA submitted to the IASP 2018 and 2020 workshops. Methods The IASP distributed uniquely coded sera from individuals with new-onset type 1 diabetes, multiple islet autoantibodypositive individuals, and diabetes-free blood donors in both 2018 and 2020. Serial dilutions of the anti-insulin mouse monoclonal antibody HUI-018 were also included. Sensitivity, specificity, area under the receiver operating characteristic curve (ROCAUC), partial ROC-AUC at 95% specificity (pAUC95) and concordance of qualitative/quantitative results were compared across Results Results from 45 IAA assays of seven different formats and from 37 IAA assays of six different formats were submitted to the IASP in 2018 and 2020, respectively. The median ROC-AUC was 0.736 (IQR 0.617–0.803) and 0.790 (IQR 0.730–0.836), while the median pAUC95 was 0.016 (IQR 0.004–0.021) and 0.023 (IQR 0.014–0.026) in the 2018 and 2020 workshops, respectively. Assays largely differed in AUC (IASP 2018 range 0.232–0.874; IASP 2020 range 0.379–0.924) and pAUC95 (IASP 2018 and IASP 2020 range 0–0.032). Conclusions/interpretation Assay formats submitted to this study showed heterogeneous performance. Despite the high variability across laboratories, the in-house radiobinding assay (RBA) remains the gold standard for IAA measurement. However, novel non-radioactive IAA immunoassays showed a good performance and, if further improved, might be considered valid alternatives to RBAs.

Keywords Autoantibodies . IAA . IASP interlaboratory comparison study . Sensitivity . Specificity . Type 1 diabetes

Ilaria Marzinotto and David L. Pittman contributed equally.

Alistair John Kerr Williams died on 17th September 2020.

* Peter Achenbach

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* Vito Lampasona

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1 San Raffaele Diabetes Research Institute, San Raffaele Scientific Institute, Milan, Italy

2 Department of Pathology, University of Florida, Gainesville, FL, USA

3 Diabetes and Metabolism, Translational Health Sciences, University of Bristol, Bristol, UK

4 Institute of Diabetes Research, Helmholtz Munich, German Research Center for Environmental Health, Neuherberg, Germany

5 Department of General Surgery, Visceral, Thoracic and Vascular Surgery, University Medical Center Greifswald, Greifswald, Germany

6 Institute of Pathophysiology, Research Group of Predictive Diagnostics, University Medical Center Greifswald, Karlsburg, Germany

7 Division of Diabetes, Endocrinology, and Metabolic Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, USA

https://doi.org/10.1007/s00125-023-05877-9 / Published online: 10 February 2023

Embracing complexity: making sense of diet, nutrition, obesity and type 2 diabetes

Nita G. Forouhi1

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1 MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, UK

Received: 27 July 2022 /Accepted: 13 December 2022 / Published online: 14 February 2023 © The Author(s) 2023

Abstract

      Nutrition therapy has been emphasised for decades for people with type 2 diabetes, and the vital importance of diet and nutrition is now also recognised for type 2 diabetes prevention. However, the complexity of diet and mixed messages on what is unhealthy, healthy or optimal have led to confusion among people with diabetes and their physicians as well as the general public. What should people eat for the prevention, management and remission of type 2 diabetes? Recently, progress has been made in research evidence that has advanced our understanding in several areas of past uncertainty. This article examines some of these issues, focusing on the role of diet in weight management and in the prevention and management of type 2 diabetes. It considers nutritional strategies including low-energy, low-fat and low-carbohydrate diets, discusses inter-relationships between nutrients, foods and dietary patterns, and examines aspects of quantity and quality together with new developments, challenges and future

Keywords Diet . Epidemiology . Nutrients . Nutrition . Obesity . Quality . Quantity . Review . Study design . Type 2 diabetes

Abbreviations

DASH Dietary Approaches to Stop Hypertension

GI Glycaemic index

GL Glycaemic load

NHS National Health Service

Causal factors underlying diabetes risk informed by Mendelian randomisation analysis: evidence, opportunities and challenges

Shuai Yuan1 & Jordi Merino2,3,4,5 & Susanna C. Larsson1,6

Received: 5 October 2022 /Accepted: 4 January 2023 / Published online: 14 February 2023

© The Author(s) 2023

Abstract

      Diabetes and its complications cause a heavy disease burden globally. Identifying exposures, risk factors and molecular processes causally associated with the development of diabetes can provide important evidence bases for disease prevention and spur novel therapeutic strategies. Mendelian randomisation (MR), an epidemiological approach that uses genetic instruments to infer causal associations between an exposure and an outcome, can be leveraged to complement evidence from observational and clinical studies. This narrative review aims to summarise the evidence on potential causal risk factors for diabetes by integrating published MR studies on type 1 and 2 diabetes, and to reflect on future perspectives of MR studies on diabetes. Despite the genetic influence on type 1 diabetes, few MR studies have been conducted to identify causal exposures or molecular processes leading to increased disease risk. In type 2 diabetes, MR analyses support causal associations of somatic, mental and lifestyle factors with development of the disease. These studies have also identified biomarkers, some of them derived from the gut microbiota, and molecular processes leading to increased disease risk. These studies provide valuable data to better understand disease pathophysiology and explore potential therapeutic targets. Because genetic association studies have mostly been restricted to participants of European descent, multi-ancestry cohorts are needed to examine the role of different types of physical

Susanna C. Larsson

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1 Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden

2 Diabetes Unit and Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA

3 Programs in Metabolism and Medical and Population Genetics, Eli and Edythe L. Broad Institute of MIT and Harvard, Cambridge, MA, USA

4 Department of Medicine, Harvard Medical School, Boston, MA, USA

5 Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

6 Unit of Medical Epidemiology, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden activity, dietary components, metabolites, protein biomarkers and gut microbiome in diabetes development.

Keywords Causality . Diabetes . Mendelian randomisation . Review . Risk factor

Vacuum-assisted closure versus conventional dressing in necrotizing fasciitis: a systematic review and meta-analysis

Rongli Zhang, Yahui Zhang, Liyuan Hou and Chengyong Yan*

Abstract

Background Necrotizing fasciitis is a rapid and severe soft tissue infection that targets subcutaneous fat tissue, muscle, and fascia. This study compares the clinical outcomes of vacuum-assisted closure (VAC) versus conventional dressing on necrotizing fasciitis.

Methods We systematically searched Embase, Cochrane, and PubMed for clinical trials (published between January 1, 1995 and September 30, 2021), which compared VAC with conventional dressing for necrotizing fasciitis. The mortality rate of necrotizing fasciitis was the primary outcome of this study. The number of debridements, the total length of hospital stay, and the complication rate were secondary outcomes. A random effects model assessed all pooled

Results A total of 230 identified studies and seven controlled clinical trials met the inclusion criteria and were included in this analysis (n =249 participants). Compared to the conventional dressing, patients treated with VAC had a significantly lower mortality rate [OR =0.27, 95% CI (0.09, 0.87)] (P=0.03). Total length of hospital stays [MD=8.46, 95% CI (− 0.53, 17.45)] (P=0.07), number of debridements [MD =0.86, 95% CI (− 0.58, 2.30)] (P=0.24), and complication rate [OR=0.64, 95% CI (0.07, 5.94)] (P=0.69) were not significant. These results did not show significant diferences between both groups treated with VAC or conventional treatment.

Conclusion VAC could significantly decrease the death rate compared to conventional dressing. No significant impacts were found on the number of debridements, the total length of hospital stay, and the complication rate in this study. Level of evidence Level-III. Registration Research Registry (reviewregistry1246).

Keywords Necrotizing fasciitis, Vacuum-assisted closure, Conventional dressing, Meta-analysis

*Correspondence:

Chengyong Yan

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Department of Orthopaedic Surgery, Third Hospital of Hebei Medical

University, Shijiazhuang, China

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