Stephen M Twigg

Stephen M Twigg
University of Sydney and Royal Prince Alfred Hospital (RPAH) · Sydney Medical School, Charles Perkins Centre, and Dept of Endocrinology

MBBS(Hons-I) PhD FRACP

About

326
Publications
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Introduction
Skills and Expertise

Publications

Publications (326)
Article
Full-text available
Background Diabetes-related foot disease (DFD) is a leading cause of the Australian disease burden. The 2011 Australian DFD guidelines were outdated. We aimed to develop methodology for systematically adapting suitable international guidelines to the Australian context to become the new Australian evidence-based guidelines for DFD. Methods We foll...
Article
Full-text available
Background Diabetes-related foot ulceration (DFU) has a substantial burden on both individuals and healthcare systems both globally and in Australia. There is a pressing need for updated guidelines on wound healing interventions to improve outcomes for people living with DFU. A national expert panel was convened to develop new Australian evidence-b...
Article
Full-text available
It is unclear if cutaneous microvascular dysfunction associated with diabetes and obesity can be ameliorated with exercise. We investigated the effect of 12-weeks of exercise training on cu-taneous microvascular reactivity in the foot. Thirty-three inactive adults with type 2 diabetes and obesity (55% male, 56.1 ± 7.9 years, BMI: 35.8 ± 5, diabetes...
Article
Background There is growing interest in Food is Medicine programs that incorporate food-based interventions into health care for patients with diet-related conditions. Objectives We aimed to test the feasibility of a “produce prescription” program and its impact on diet quality for people with type 2 diabetes (T2D) experiencing food insecurity in...
Article
Full-text available
Background Peripheral artery disease (PAD) is implicated in up to 50% of diabetes-related foot ulcers (DFU) and significantly contributes to morbidity and mortality in this population. An evidence-based guideline that is relevant to the national context including consideration of the unique geographical and health care system differences between Au...
Article
Aims: To identify biomarkers of cardiomyopathy in patients with type 2 diabetes mellitus (T2DM) using cardiovascular magnetic resonance (CMR) and to identify associations between functional status, metabolomic profile and myocardial fibrosis. Methods: In this prospective case control study, patients (n = 49) with T2DM without significant coronar...
Article
Aims Diabetes mellitus is a state of chronic low-grade inflammation. Scavenger receptor CD163, expressed on monocyte/macrophage cells with anti-inflammatory functions, has been observed in diabetes complications. This review aimed to systematically survey human studies published until 31st January 2022 for CD163 expression, in particular diabetes c...
Article
Full-text available
A diet-induced non-alcoholic fatty liver disease (NAFLD) model causing obesity in rodents was used to examine whether sitagliptin and gliclazide therapies have similar protective effects on pathological liver change. Methods: Male mice were fed a high-fat diet (HFD) or standard chow (Chow) ad libitum for 25 weeks and randomly allocated to oral si...
Article
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Background Short-chain fatty acids (SCFAs) produced by the gut microbiota have beneficial anti-inflammatory and gut homeostasis effects and prevent type 1 diabetes (T1D) in mice. Reduced SCFA production indicates a loss of beneficial bacteria, commonly associated with chronic autoimmune and inflammatory diseases, including T1D and type 2 diabetes....
Article
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Type 2 diabetes is an independent risk factor for non-alcoholic steatohepatitis (NASH) progression and its mediators have not been resolved. In this study, a pathogenic role of cellular communication network factor 2 (CCN2) protein in NASH pathology, was investigated in an established preclinical NASH model. Male wild type C57BL/6 mice received eit...
Article
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(1) Background: studies on the long-term dynamic changes in fat depot metabolism in response to a high-fat diet (HFD) on hepatic lipid deposition and insulin resistance are sparse. This study investigated the dynamic changes produced by HFD and the production of dysfunctional fat depots on insulin resistance and liver lipid metabolism. (2) Methods:...
Article
Full-text available
Background Conservative sharp wound debridement (CSWD) is fundamental to wound bed preparation. Evidence-based practice guidelines strongly recommend frequent CSWD of diabetes-related foot ulcers (DFU) based on expert opinion and observational studies which suggest that more frequent debridement is associated with better healing outcomes. Aim To d...
Article
Full-text available
Background Wound classification systems are useful tools to characterise diabetes-related foot ulcers (DFU) and are utilised for the purpose of clinical assessment, to promote effective communication between health professionals, and to support clinical audit and benchmarking. Australian guidelines regarding wound classification in patients with DF...
Article
Aim This systematic review aimed to determine the effect of aerobic exercise interventions, including high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT), on liver fat in adults. A secondary aim was to investigate the interaction between total weekly exercise volume and exercise-related energy expenditure and c...
Article
Full-text available
Introduction Diabetes-related foot disease is a large cause of the global disease burden yet receives very little research funding to address this large burden. To help address this gap, it is recommended to first identify the consensus priority research questions of relevant stakeholders, yet this has not been performed for diabetes-related foot d...
Article
The incidence of type 2 diabetes (T2D) is increasing globally, with long-term implications for human health and longevity. Heart disease is the leading cause of death in T2D patients, who display an elevated risk of an acute cardiovascular event and worse outcomes following such an insult. The underlying mechanisms that predispose the diabetic hear...
Preprint
Background: Short chain fatty acids (SCFAs) produced by the gut microbiota have beneficial anti-inflammatory and gut homeostasis effects and prevent type 1 diabetes (T1D) in mice. Reduced SCFA production indicates a loss of beneficial bacteria (dysbiosis), commonly associated with chronic autoimmune and inflammatory diseases, including T1D and type...
Article
Diet and/or exercise are cost effective interventions to treat obesity. However, it is unclear if the type of exercise undertaken can prevent the onset of obesity and if it can act through different effects on fat depots. In this study we did not allow obesity to develop so we commenced the high-fat diet (HFD) and exercise programs concurrently and...
Article
Background Young-onset type 2 diabetes is an aggressive disease characterized by development of diabetic complications, including nephropathy, early in the disease course. However, within the cohort of young-onset type 1 and type 2 diabetes there are limited comparative data regarding progression to ESKD requiring renal replacement therapy or renal...
Article
Background Studies examining hypercalcaemia in inpatients were largely published over 20 years ago, and it is likely the epidemiology of hypercalcaemia has changed related to increased lifespan and changes in prevalence of the underlying causes such as malignancy. Aim To explore the epidemiology of hypercalcaemia in a modern tertiary hospital sett...
Article
In prediabetes (PD), circulating inflammatory biomarkers are associated with increased CVD1 risk. Exercise (Ex) has a positive effect on cardiovascular fitness and metabolic outcomes in PD but Ex effects on inflammation markers in PD are not fully known and were investigated in this study. Adults with PD (n=34) and normal fasting glucose (NG) (n=34...
Article
Introduction: CCN2, formerly known as CTGF, is a pro-fibrotic protein that is implicated in several diabetes-related complications. The role of CCN2 in mediating NASH fibrosis in diabetes has not been fully elucidated. We hypothesize that targeting liver CCN2 can prevent NASH fibrosis in diabetes. Aim: To examine whether hepatocyte specific homozyg...
Article
Full-text available
Diet and/or exercise are cost effective interventions to treat obesity. However, it is unclear if the type of exercise undertaken can prevent the onset of obesity and if it can act through different effects on fat depots. In this study we did not allow obesity to develop so we commenced the high-fat diet (HFD) and exercise programs concurrently and...
Article
Full-text available
Background: Exercise-induced improvements in cardiorespiratory fitness (CRF) often coincide with improvements in insulin sensitivity and reductions in liver fat content. However, there are limited data concerning the relationship between CRF and liver fat content in adults with varying degrees of metabolic dysfunction. Methods: The aim of this s...
Article
Aims Delayed healing of diabetes-related foot ulcers (DRFUs) is associated with increased macrophage and matrix metalloproteinases (MMPs) at the wound site. Whether circulating monocyte phenotype and/or MMPs are altered in association with wound healing outcome is unknown, and was investigated in this study. Methods Blood was obtained from 21 part...
Article
Backgrounds and Aims Obesity and diabetes independently contribute to cutaneous microvascular dysfunction via pathological processes that are not fully understood. We sought to determine if obesity severity is associated with cutaneous microvascular dysfunction and measures of peripheral arterial disease in adults with type 2 diabetes in cross-sect...
Article
Background: Clinic attendance, metabolic control, engagement in self-management and psychological health are suboptimal in young-onset (<40 years) type 2 diabetes. Objective: We examined the effectiveness of an enhanced SMS-based support and reminder program in improving clinic attendance, metabolic control, engagement in self-management and psy...
Preprint
BACKGROUND Clinic attendance, metabolic control, engagement in self-management, and psychological health are suboptimal in young-onset (age of onset <40 years) type 2 diabetes. OBJECTIVE We examined the effectiveness of an enhanced SMS text message–based support and reminder program in improving clinic attendance, metabolic control, engagement in...
Chapter
Endocrine manifestations of substance use disorders can result from the direct effect of the addictive substance, chronic and acute toxicological phenomena, or more indirectly due to long-term disturbances of delicate hormonal feedback loops. Although the existing data is largely based on case reports and animal studies, emerging evidence suggests...
Article
Background To assess the association between body composition and the risk of adverse outcomes in Fontan patients. Methods Participants from the Australian and New Zealand Fontan Registry with dual-energy X-ray absorptiometry scans were included. Appendicular lean mass (ALM), appendicular lean mass index (ALM divided by height squared; ALMI) and t...
Conference Paper
Introduction: Increased adiposity and reduced lean mass are prevalent in Fontan patients and could be impactful because of the reliance on the peripheral muscle pump and the importance of favourable pulmonary physiology in univentricular physiology. The current study aimed to determine the impact of body fat and lean mass on the risk of adverse out...
Article
Full-text available
The increasing consumption of high-fat foods combined with a lack of exercise is a major contributor to the burden of obesity in humans. Aerobic exercise such as running is known to provide metabolic benefits, but how the over-consumption of a high fat diet (HFD) and exercise interact is not well characterized at the molecular level. Here, we exami...
Preprint
Full-text available
Background: Exercise-induced improvements in cardiorespiratory fitness (CRF) often coincide with improvements in insulin sensitivity and intrahepatic lipid content (IHL). The aim of this study was to examine the association between CRF, IHL, and insulin resistance in inactive adults with obesity and with or without type 2 diabetes, via cross-sectio...
Article
Background Telomeres are essential DNA-protein complexes whose attrition results in cellular dysfunction and senescence. Leucocyte telomere length (LTL) correlates with tissue telomere length, representing a biomarker for biological age. However its predictive value for mortality risk, and for cardiovascular vs cancer deaths, in older adults remain...
Article
Aim To assess the prevalence of metabolic syndrome in type 1 diabetes, and its age‐related association with diabetes complications. Methods Australian National Diabetes Information Audit and Benchmarking (ANDIAB) was a well‐established quality audit programme. It provided cross‐sectional data on people attending specialist diabetes services across...
Article
Aim To systematically evaluate research investigating the accuracy of the ankle–brachial index (ABI) for diagnosing peripheral artery disease (PAD) in people with diabetes, as the accuracy is thought to be reduced in this cohort. Methods A database search of EBSCO Megafile Premier, Embase and The Cochrane Library was conducted to 28 February 2019....
Article
Full-text available
Objective: The aim of this study was to examine the effect of a novel low-volume high- intensity interval training (HIIT), moderate-intensity continuous training (MICT) or placebo (PLA) intervention on liver fat, glycaemia, and cardiorespiratory fitness using a randomised placebo-controlled design. Research design and methods: Thirty-five inactive...
Article
Full-text available
Context: Research has described that adiponectin plays a key role in cardiomyocytes metabolism, however, the effects of exercise during obesity on cardiac adiponectin levels is unclear. Objective: To investigate the effects of constant-moderate endurance (END) and high-intensity interval training (HIIT), on heart adiponectin levels in mice. Mater...
Article
Background Interventions involving both exercise and dietary modification are effective in reducing steatosis in NAFLD. However, exercise alone may reduce liver fat and is known to have other positive effects on health. The primary aim of this study was to systematically review the effect of exercise alone without dietary intervention on NAFLD and...
Article
OBJECTIVE: To study the effect of 12 weeks of high-intensity interval training (HIIT) on glycemic control in adults with type 1 diabetes and overweight or obesity. RESEARCH DESIGN AND METHODS: Thirty inactive adults with type 1 diabetes who had BMI ≥25 kg/m2 and HbA1c ≥7.5% were randomized to 12 weeks of either HIIT exercise intervention consistin...
Article
This review investigated the association of periodontal disease with diabetes mellitus (DM) and diabetic complications. PubMed/MEDLINE was searched including search terms “periodontal” OR “periodontitis” AND “diabetic complications” OR “diabetic retinopathy” OR “diabetic nephropathy” OR “diabetic neuropathy” OR “cardiovascular disease diabetes” OR...
Article
Impaired angiogenic responses to ischemia characterize the vascular complications associated with diabetes. Diabetic foot ulcers in the presence of ischemia are associated with the most severe outcomes, including a higher rate of mortality and lower probability of healing. Specific micro-RNAs (miRNAs) such as miRNA-200b have been shown to negativel...
Article
Zinc is required for activation of Matrix Metalloproteinases (MMPs). Circulating zinc levels are decreased in diabetes1 and decreased activity of some MMPs is associated with the development of diabetic nephropathy (DN). The association between MMP activity and zinc in the development of DN has not been investigated and was examined in a preclinica...
Article
Background Low-volume high-intensity interval training (HIIT) may be a time-efficient strategy that leads to similar or superior improvements in cardiorespiratory fitness (CRF) and cardiovascular disease (CVD) risk factors when compared with moderate-intensity continuous training (MICT). Our study investigated the effect of low-volume HIIT or MICT...
Article
Full-text available
Transforming growth factor beta (TGFβ) a multifunctional cytokine is known to regulate cell proliferation, differentiation, migration and survival. Although there is variable expression of modulators of TGFβ action during differentiation, a differential effect on fat cell metabolism at different stages of adipocyte differentiation was unclear. In t...
Article
Full-text available
Background We sought to characterize body composition abnormalities in young patients living with a Fontan circulation and explore potential pathophysiologic associations. Methods and Results Twenty‐eight patients with a Fontan circulation were prospectively recruited in this cross‐sectional study. Participants underwent cardiopulmonary exercise t...
Article
Full-text available
Background Individuals with diabetes have greater central arterial stiffness, wave reflections, and hemodynamics, all of which promote the accelerated cardiovascular pathology seen in this population. Acute aerobic exercise has been shown to be an effective strategy for reducing central arterial stiffness, wave reflections, and hemodynamics in heal...
Article
Full-text available
Aims: To examine the possibility of a residual increased susceptibility to complications in people with young-onset type 2 diabetes as compared to those with later-onset disease. Methods: Prospective data from 3322 individuals, diagnosed between the age of 15 and 70 years and collected 10-25 years after diabetes diagnosis, were analysed. The cro...
Article
Full-text available
Background: Apolipoprotein-AI (apo-AI) is the major apolipoprotein found in high density lipoprotein particles (HDLs). We previously demonstrated that apo-AI injected directly into high-fat diet fed mice improved insulin sensitivity associated with decreased hepatic inflammation. While our data provides compelling proof of concept, apoA-I mimetic...
Article
An 18-year-old woman with a history of hollow visceral myopathy presented with a small-bowel obstruction. High-dose opioid analgesia was required subsequently during hospital admission. She suffered two episodes of documented fasting hypoglycaemia, despite adjustment of parenteral carbohydrate administration. Investigations for non-insulin-mediated...
Article
Aims: We aimed to examine the feasibility and safety of undertaking high-intensity interval exercise (HIIE) with evening basal insulin dose reduction on exercise-related hypoglycaemia following an afternoon bout of HIIE, compared with moderate-intensity continuous exercise and a non-exercise control day in adults with type 1 diabetes in a free-liv...
Article
Objective: Effects of insulin-like growth factor 1 (IGF1) and its binding proteins (IGFBPs) on ageing, and their interaction with sex hormones, remain uncertain. We examined associations of plasma IGF1, IGFBP1, IGFBP3, estradiol and testosterone, with leucocyte telomere length (LTL), a marker of biological age, in 2999 community-dwelling men aged 7...
Article
Full-text available
Background: Advances in information communications technology (ICT) provide opportunities for enhanced diabetes care. Knowledge of the more acceptable communication modalities in patients of different ages will help to inform the direction of future innovations. Methods: An anonymous ICT survey (examining access and use of mobile phones, compute...
Article
Objective: The American Diabetes Association recommends individuals with type 1 diabetes (T1D) adjust insulin for dietary fat; however, optimal adjustments are not known. This study aimed to determine 1) the relationship between the amount and type of dietary fat and glycemia and 2) the optimal insulin adjustments for dietary fat. Research design...
Article
Objective and patients: This study aimed to characterize bone mineral density abnormalities and pathophysiological associations in young adults living with a Fontan circulation. Design: Participants underwent bone mineral density measurement using dual-energy X-ray absorptiometry and serum biochemical analysis, cardiopulmonary exercise and stren...
Article
Full-text available
Objective: To investigate the associations of Graves' disease (GD) severity, autoimmunity and longitudinal liver enzyme changes with time in a cohort with well-characterized GD. Design: Retrospective cohort study. Patients: Patients diagnosed with Graves' disease, treated at Royal Prince Alfred Hospital Sydney, Adult Thyroid Clinic from 2000 t...
Article
People with diabetes mellitus have shorter telomeres compared with non-diabetic subjects. The aim of this study was to investigate an in-vitro model of telomere shortening under diabetes metabolic conditions. The mechanisms of the accelerated telomere length attrition and the potential telomere protective action of fenofibrate with related cellular...