Diabetes, Exercise and Liver Fat (DELIVER) - Version 1
Research type
Research Study
Full title
The Impact of Type 2 Diabetes and Exercise on Liver Fat Quality
IRAS ID
241046
Contact name
James King
Contact email
Sponsor organisation
Loughborough University
Duration of Study in the UK
2 years, 0 months, 0 days
Research summary
Summary of Research
Non-alcoholic fatty liver disease (NAFLD) is a health condition characterised by an excessive accumulation of liver fat which often occurs in response to obesity. Liver fat is positively associated with insulin resistance and high levels predispose individuals to develop type 2 diabetes (T2DM). Problematically, T2DM is known to promote a more aggressive disease trajectory in people with NAFLD; elevating the risk of developing non-alcoholic steatohepatitis (liver inflammation), liver fibrosis (scar tissue) and liver cancer. Recent research has suggested that not all liver fat is equal, with saturated fats, rather than unsaturated fats, driving the unhealthy metabolic profile associated with NAFLD. The aim of this study is two-fold: 1) to determine whether liver fat quality is associated with the more severe metabolic health profile seen in individuals with NAFLD and T2DM compared to non-diabetic individuals with NAFLD; 2) to determine whether exercise training can favourably module liver fat quality in individuals with NAFLD and T2DM.This research contains a cross-sectional study (Part A) and a randomised intervention (Part B). In Part A, liver fat quality (saturated, unsaturated and polyunsaturated fat indices) and associated metabolic, physiological and anthropometric factors will be compared between obese men with NAFLD (n = 14) versus obese men with NAFLD and T2DM (n = 26). In Part B, the recruited sample of obese men with NAFLD and T2DM will be randomised (1:1) to a six week intervention or control group (n = 13 per group). Those randomised to the intervention will undertake six weeks of moderate-intensity exercise training (150 – 200 min per week) that will involve three supervised and one unsupervised sessions each week. Post-intervention assessments will occur 48 h after the last exercise training session.
This research is supported by a Diabetes UK Early Career Research Grant and funding provided by the NIHR Nottingham and Leicester Biomedical Research Centres.
Summay of Results
This study investigated the impact of type 2 diabetes and exercise on liver fat quality (i.e. proportion of saturated, unsaturated and polyunsaturated fat) in men with non-alcoholic fatty liver disease (NAFLD). The first part of the study compared liver fat quality between a group of men with NAFLD but normal blood sugar control and a group of men with NAFLD and impaired blood sugar control. The second part of the study looked to see if 6 weeks of exercise training can change liver fat quality in the group of men with NAFLD and impaired blood sugar control.Why was the research done?
Having high amounts of liver fat (NAFLD) is linked to poorer blood sugar control and a higher risk of developing type 2 diabetes. However, it has recently been suggested that not all fat stored in the liver may be harmful and instead the type of fat (liver fat quality) may determine the health risks associated with NAFLD. Therefore, we wanted to see if liver fat quality was different in men with NAFLD with either normal or impaired blood sugar control. A previous study has also shown that short-term exercise (7 days of walking) may be able to improve liver fat quality by increasing the proportion of ‘healthier’ fats (polyunsaturated fat) in the liver. Therefore, we wanted to see if longer-term exercise training (6 weeks) was able to improve liver fat quality in the group of men with NAFLD and impaired blood sugar control.
Who conducted the research?
The study was conducted by researchers from Loughborough University in collaboration with other researchers from the Leicester Diabetes Research Centre, University of Nottingham and UHL & NUH NHS Trusts. The research was funded by Diabetes UK and the Leicester and Nottingham NIHR Biomedical Research Centres.
What did the research study involve?
The study recruited 40 men aged between 30-75 years with NAFLD (confirmed by an MRI scan) in the East Midlands region of the UK. The participants were then split into 2 groups depending on whether they had normal blood sugar control (glycated haemoglobin < 42 mmol/mol; 14 in total) or impaired blood sugar control (glycated haemoglobin > 42 mmol/mol; 26 in total).
Study visits took place at the Sir Peter Mansfield Imaging Centre, Leicester Diabetes Centre and Queens Medical Centre between October 2018 and July 2022. Eligibility was confirmed at the first study visit which involved an MRI scan to measure liver fat quality (proportions of saturated, unsaturated and polyunsaturated fat) and other health measurements such as weight, blood pressure and body fat percentage. At the second study visit, participants’ fitness level was measured by a maximal walking test and a blood sample was taken to measure glycated haemoglobin levels as well as other health biomarkers including markers of liver function and injury (CK18).
The group with impaired blood sugar control were then randomised to take part in one of two 6-week interventions: moderate-intensity walking/cycling exercise or control (continuing normal habits). The exercise training involved four 35-50-minute sessions (1 supervised) per week for 6 weeks. At the end of the 6-week exercise and control interventions, the two study visits were repeated to assess how their liver fat quality and other health outcomes had changed.
What were the results of the study?
The main findings of the first part of the research study were that the group with NAFLD and impaired blood sugar control tended to have a higher proportion of saturated liver fat and lower proportion of unsaturated liver fat compared to the group with normal blood sugar control. Blood levels of CK18 M65 (an indicator of liver injury) were also higher in the group with impaired versus normal blood sugar control. These factors were directly associated with worse blood sugar control and insulin resistance.
The main findings of the second part of the study were that six-weeks of exercise training largely did not alter liver fat composition in men with NAFLD and impaired blood sugar control. However, there were subtle indications that exercise training produced small reductions in the proportion of saturated liver fat and increases in the proportion of unsaturated liver fat. We also found that the people who improved their fitness the most with exercise training also saw the biggest reductions in saturated liver fat and increases in unsaturated and polyunsaturated liver fat.
How has this study helped patients and researchers?
The most important finding from our project is that people living with high blood sugar levels or type 2 diabetes have fat in their livers which is composed of more saturated (and less unsaturated) fats, providing more evidence that type 2 diabetes is a condition that damages the liver. Doctors and researchers are becoming increasingly aware of the connection between diabetes and the liver, and our data will help to raise awareness so that diabetes specialists more closely monitor patients’ liver health. This means that doctors may perform more thorough screening of patients to detect liver disease earlier, and also provide more specific treatments for more advanced liver problems.
Where can I learn more about this study?
More information on the research study can be found at the following links:
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We would like to thank all of the participants who took part in the research study.
REC name
East Midlands - Nottingham 1 Research Ethics Committee
REC reference
18/EM/0161
Date of REC Opinion
23 Jul 2018
REC opinion
Further Information Favourable Opinion