Researchers at the Diamantina Institute and the PA Hospital sincerely thank you for participating in our previous clinical studies. Without your support and willingness, we could not have produced these results.
The effect of a 4 month lifestyle intervention on muscle fat utilisation during exercise in obese males
Accumulation of intramyocellular lipids (IMCL), fat in muscle cells, is an early phenomenon in the development of insulin resistance and diabetes. Paradoxically, insulin sensitive endurance trained individuals also have elevated IMCL and can use these as a substrate source during exercise. We used magnetic resonance spectroscopy (MRS) in 18 obese non-diabetic men to investigate the mobilisation of IMCL of soleus muscle during exercise before and after a 4 month lifestyle intervention including exercise and diet.
Results
The average weight loss was 8.6 ± 4.5% of body weight (10.0 ± 5.4 kg) (p<0.001). This was accompanied by an average improvement in insulin resistance (homeostasis model assessment (HOMA)) of 0.9 ± 2.0, an increase in VO2max (fitness) of 5.2 ± 3.4 mLO2.kg-1.min-1 and an increase in body fat oxidation of 0.19 ± 0.22 g/.min-1 (p<0.05 for all). Although, we measured no mobilisation of IMCL during the exercise session either before or after the lifestyle intervention. This suggests that a successful lifestyle intervention which results in weight loss does not improve mobilisation of IMCL during acute exercise within a group of obese men.
The effect of a 4 month lifestyle intervention on the distribution of body fat in obese males
Visceral adipose tissue (VAT), intrahepatic lipids (IHL) and intramyocellular lipids (IMCL) are associated with increased risk of type 2 diabetes. We investigated the role of weight loss through diet and exercise in modulating these excess lipid stores in 18 obese non-diabetic males. Total body fat, VAT, IHL and IMCL were measured using Dual energy X-ray absorptiometry (DEXA), magnetic resonance imaging (MRI) and spectroscopy (MRS). Insulin sensitivity was assessed using homeostasis model assessment (HOMA). Exercise sessions were recorded with a heart rate monitor and dietary intake monitored by three day diet diaries.
Results
During the intervention, subjects averaged 1902 ± 1503 kcal of exercise per week, VO2max increased by 5.2 ± 3.4 ml•kg-1•min-1 (p<0.001) and HOMA decreased by 0.9 ± 2.0 (p<0.05). Total body fat decreased by 20 ± 12%, VAT by 29 ± 18% and IHL by 54 ± 30% (all p<0.001), while IMCL did not change significantly. Subjects who exercised more had a greater decrease in VAT (p=0.04). Insulin resistance correlated with IHL before and after the intervention (p<0.05), but was not associated with VAT or IMCL. Reduction in IHL was associated with decreases in plasma lipids (total/HDL-cholesterol, VLDL and triglycerides (p<0.05)). In summary, different regions of fat in the body react to different types of intervention and not all fat are associated with metabolic dysfunction in the same way.
HPV in normal verses sun-exposed skin
Human papillomaviruses (HPV) have been widely detected in healthy skin and are considered to be part of the normal flora of the skin. Previous studies have found that UV radiation can activate several HPV types, and a higher frequency of HPV types have been detected from body sites that are more often exposed to the sun. A possible role for HPV in the development of non-melanoma skin cancer has been suggested. This study investigated the occurrence of HPV on the skin in relation to UV exposure.
The study was carried out in 2007 by analysing forehead skin swab samples from 50 healthy Brisbane male road workers who spend their working hours outdoors and comparing this to 50 healthy male laboratory scientists who spend working hours indoors. A questionnaire, including ethnic background of the participants, history of cancers, and a self-assessment of sun-exposure, was also conducted and analysed.
Results
We found HPV occurred more often in people who spent more time outdoors and in individuals with a history of skin cancers. Surprisingly, if you wore sunglasses as a means of sun protection you had a lower prevalence of HPV. Finally, one particular HPV type (type 76) was only detected in indoor workers. These results suggest that increased UV radiation exposure may be a factor leading to a difference in prevalence of HPV types.
The value of the histone deacetylase inhibitor, valproate, in treating patients with head and neck squamous cell carcinomas
This trial was conducted by Dr’s Alexander Guminski, Rafael Erlich and Nicholas Saunders. In this trial, patients with advanced or unresectable head and neck cancers were administered oral valproate for a 2-4 week period and the tumour progression/regression monitored. In total 6 patients were enrolled in this early phase trial.
Results
We found that the response to valproate was variable and there were clinical signs of a response in some patients as well as biochemical signs that the valproate was having the desired inhibitory effect on histone deacetylase activity. However, the overall conclusion was that a) it would not be possible to achieve high enough doses of valproate in these patients to act as an effective monotherapy and b) combinations of an histone decaetylase inhibitor with other drugs such as cisplatin are likely to have more efficacy against head and neck cancers.
Atherosclerotic disease is increased in recent onset rheumatoid arthritis
Rheumatoid arthritis patients are at increased risk of heart attack, stroke and early death as a result of cardiovascular and cerebro-vascular disease (atherosclerosis). We carried out this study to determine how early this accelerated atherosclerosis begins in rheumatoid arthritis, and how soon risk factors must be controlled. Carotid intima-media thickness (cIMT) and plaque, measured by ultrasound, correlate closely with direct measurement of local and systemic atherosclerotic burden. To investigate the presence of atherosclerosis in patients without known atherosclerotic disease in the early stages of rheumatoid arthritis, cIMT and plaque were measured using carotid duplex scanning in 40 rheumatoid arthritis patients with disease duration of less than 12 months and 40 control subjects matched for age, sex and established cardiovascular risk factors.
Results
Patients with rheumatoid arthritis had significantly higher average cIMT values and more plaque than the control group. In rheumatoid arthritis patients, cIMT was predicted by age and C-reactive protein (CRP, a measure of inflammation) level at first presentation to the clinic. CRP was associated with age of disease onset and history of smoking. We speculate that since inflammation has been shown to predate onset of clinical rheumatoid arthritis, the accelerated atherogenic process related to inflammation may precede rheumatoid arthritis symptom onset.
Reference
Hannawi S, Haluska B, Marwick TH, and R Thomas. (2007) “Atherosclerotic disease is increased in recent onset rheumatoid arthritis: a critical role for inflammation.” Arthritis Res Ther 9:R116.
See also editorial: Veldhuijzen van Zanten JJCS, Kitas GD. (2008) “Inflammation, carotid intima-media thickness and atherosclerosis in rheumatoid arthritis.” Arthritis Res Ther 10:102.