Adiposity
Conditions
Brief summary
This pilot study investigates the relationship between type 2 diabetes (T2D) and adipose tissue dysfunction across different ethnic groups. Adipose tissue dysfunction is characterised by abnormal fat distribution, including increased visceral, hepatic, and pancreatic fat, elevated inflammatory biomarkers, and impaired metabolic function. T2D is a chronic metabolic disease characterised by insulin resistance and disrupted glucose regulation. In the UK, its prevalence is significantly higher among South Asian and Black African/Caribbean populations than among White Europeans. Differences in adipose tissue distribution, particularly increased visceral fat accumulation, are thought to contribute to this disparity. Adipose tissue dysfunction, including chronic inflammation and altered adipokine secretion, is also associated with the development and progression of T2D. Previous studies have identified ethnic differences in body fat distribution and metabolic risk. Genetic factors influencing adipose tissue function may partly explain variations in fat storage and susceptibility to T2D across populations. However, the specific contribution of adipose tissue dysfunction to ethnic differences in T2D risk remains unclear. Evidence suggests that South Asians tend to have higher levels of liver and ectopic fat and a reduced capacity for safe subcutaneous fat storage, leading to fat accumulation in metabolically harmful sites. These characteristics are associated with increased insulin resistance and T2D risk. In contrast, Black populations often exhibit lower levels of visceral fat but still experience a high prevalence of T2D, indicating that factors beyond fat quantity may contribute to disease risk. Despite extensive research on ethnic disparities in metabolic health, few studies have directly compared markers of adipose tissue dysfunction across South Asian, Black African/Caribbean, and White European populations within a single study. This study aims to address this gap and improve understanding of the mechanisms linking adipose tissue dysfunction, insulin resistance, and T2D. The findings may help inform more targeted prevention and treatment strategies for ethnically diverse populations in the UK.
Detailed description
References: 1. Amati, F., Pennant, M., Azuma, K., Dubé, J.J., Toledo, F.G.S., Rossi, A.P., Kelley, D.E. and Goodpaster, B.H. (2012). Lower Thigh Subcutaneous and Higher Visceral Abdominal Adipose Tissue Content Both Contribute to Insulin Resistance. Obesity, 20(5), pp.1115-1117. doi:https://doi.org/10.1038/oby.2011.401. 2. Goff, L M. "Ethnicity and Type 2 diabetes in the UK." Diabetic medicine : a journal of the British Diabetic Association vol. 36,8 (2019): 927-938. doi:10.1111/dme.13895 3. Iliodromiti, S. et al. (2023) "Liver, visceral and subcutaneous fat in men and women of South Asian and White European descent: A systematic review and meta-analysis of new and published data," Diabetologia, 66(1), pp. 44-56. Available at: https://doi.org/10.1007/s00125-022-05803-5. 4. Lauro, D. et al. (1998) 'Impaired glucose tolerance in mice with a targeted impairment of insulin action in muscle and adipose tissue', Nature Genetics, 20(3), p. 294. doi:10.1038/3112. 5. Unamuno, X., Gómez-Ambrosi, J., Rodríguez, A., Becerril, S., Frühbeck, G. and Catalán, V. (2018). Adipokine dysregulation and adipose tissue inflammation in human obesity. European Journal of Clinical Investigation, 48(9), p.e12997. doi:https://doi.org/10.1111/eci.12997. 6. Yaghootkar, H et al. "Ethnic differences in adiposity and diabetes risk - insights from genetic studies." Journal of internal medicine vol. 288,3 (2020): 271-283. doi:10.1111/joim.13082
Interventions
to investigate ethnic differences in adipose tissue dysfunction and its contribution to the development of type 2 diabetes mellitus in overweight and obese men from different ethnic backgrounds
to investigate ethnic differences in adipose tissue dysfunction and its contribution to the development of type 2 diabetes mellitus in overweight and obese men from different ethnic backgrounds
to investigate ethnic differences in adipose tissue dysfunction and its contribution to the development of type 2 diabetes mellitus in overweight and obese men from different ethnic backgrounds
Sponsors
Study design
Eligibility
Inclusion criteria
* Male * Aged 18-65 years * Self-identify as one of the following ethnic groups: Black African/Caribbean South Asian White European * Self-reported ancestry from the same ethnic background for at least three generations * Body Mass Index (BMI) ≥25 kg/m² and ≤40 kg/m² * Overweight or obese but otherwise generally healthy * Generally healthy, with no serious long-term medical conditions or taking medications that may alter body fat distribution * Residing in the United Kingdom * Able to understand written and spoken English * Able and willing to provide written informed consent * Willing and able to comply with all study procedures, including: * Screening assessments * Oral Glucose Tolerance Test (OGTT) * Blood sampling * Magnetic Resonance Imaging (MRI)
Exclusion criteria
* Previous diagnosis of type 1 diabetes mellitus or type 2 diabetes mellitus * HbA1c values within the diabetic range at screening * Body Mass Index (BMI) \<25 kg/m² * Presence of chronic medical conditions known to affect: * glucose metabolism * insulin sensitivity * adipose tissue distribution * inflammatory or metabolic status * History of cardiovascular, hepatic, renal, endocrine, or metabolic disease that may interfere with study outcomes or participant safety * Current use of medications known to influence: * glucose metabolism * insulin sensitivity * lipid metabolism * body composition * Current use of corticosteroids or other medications affecting metabolic function * history of substance or alcohol misuse * Contraindications to MRI, including: * metallic implants * pacemakers * severe claustrophobia * Inability to undergo venepuncture or cannulation procedures safely * Participation in another clinical or interventional research study within the previous 3 months * Inability or unwillingness to comply with study procedures or provide informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To investigate ethnic differences in glucose metabolism | Baseline and after 2 hours and 10 minutes | Dynamic glucose and insulin responses during Oral Glucose Tolerance Testing (OGTT) in mmol/L |
| To investigate ethnic differences adipose tissue dysfunction | Baseline | Regional adipose tissue distribution assessed by MRI. MRI scans will be used to measure the volume and distribution of adipose tissue in specific regions, including visceral adipose tissue (fat surrounding internal organs), subcutaneous adipose tissue (fat beneath the skin), and ectopic fat accumulation in organs such as the liver and pancreas. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To investigate ethnic differences in adipokines | Baseline | Changes in Adipokine concentrations (adiponectin, leptin, resistin) expressed in mmol/L |
| To investigate ethnic differences in inflammatory biomarkers | Baseline | Changes in Inflammatory biomarkers (TNF-α, IL-6, IL-8, IL-10, IFN-γ, MCP-1, CRP) in ng/L |
Countries
United Kingdom
Contacts
University of Roehampton