# Exercise as it relates to Disease/Diabetes: Pharmacy vs Fitness
## Background
### The Study

Knowler, W., C., Barrett-Connor, E., Fowler S., E., Hamman, R.,F., Lachin, J., M., Walker, E., A., Nathan, D., M.; Diabetes Prevention Program Research Group. (2002). Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. New England Journal of Medicine. 346(6): 393-403.

### Prevalence

Type II diabetes is a condition in which an individual becomes ineffective in addressing high blood sugar levels despite producing insulin. Type II diabetes is life threatening if left untreated, requiring lifelong management. Global prevalence of Type II diabetes is predicted to rise, with over 1 million Australians currently diagnosed. There is no current cure for type II diabetes, instead blood glucose levels are managed through medication, diet and exercise. Metformin is one such medication. Considered the number one prescribed drug for type II diabetes, Metformin is poorly prescribed for prediabetes, the precursor for type II diabetes. Fortunately, prediabetes is treatable, and with appropriate intervention, the progression to type II diabetes can be avoided.

## The Current Study
### Where Is The Research From?

The Diabetes Prevention Program Research Group is responsible for the research study. Clinical trials were conducted across 27 diabetes centres through the United States. Funding was provided by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The completed study was published in The New England Journal of Medicine.

### What Type of Research Was This?

The Research Group conducted a randomised clinical trial involving American adults classified as prediabetic (according to the American Diabetes Association). Randomised trials are effective at eliminating bias in treatment assignments so that a relationship between treatment and response may be inferred. The test group was large and culturally diverse allowing the results to be generalized toward the wider community.

### What Did The Research Involve?

A four step screening and recruiting process determined eligibility for involvement in the study, with half the participants from racial or ethnic minority groups. Exclusion criteria was applied. To be eligible, subjects must:
* Be at least 25yrs of age
* Have a Body Mass Index (BMI) of 24 or higher (22 or higher in Asians)
* Have a glucose concentration between 5.3-6.9 mmol.L$^{−1}$ in the fasting state, and between 7.8-11.0 mmol.L$^{−1}$ two hours after a 75g oral glucose load.
3234 non diabetic persons were randomly assigned one of three intervention strategies:
* Placebo twice daily plus standard lifestyle recommendations.
* Pharmaceutical (the administration of 850 mg of Metformin twice daily) plus standard lifestyle recommendations.
* Intensive program of lifestyle modification with the aim of achieving and maintain 7 percent of initial body weight through low calorie, low fat diet, and to engage in 150min of moderate intensity physical activity per week.
The primary measure of the study was the development of type II diabetes, diagnosed based upon criteria determined by the American Diabetes Association. Caloric intake was assessed using a modified version of the block food-frequency questionnaire. The placebo and pharmaceutical groups were provided with annual 20-30min individual sessions emphasising the importance of healthy lifestyle choices. The Lifestyle Intervention group were given an extensive, individualised, and culturally sensitive education program detailing diet, exercise and lifestyle choice emphasising behavioural modification. The Lifestyle Intervention group were provided continuous support highlighting the role that education plays in achieving exercise and dietary adherence.

## Outcomes
### The Basic Results

Both Metformin and Lifestyle/exercise interventions reduced the incidence of diabetes with lifestyle intervention being most effective. With an average follow up of 2.8 years, the incidence of diabetes is outlined in Table 1.2
| Intervention | Reduced Incidence of Diabetes (%) |
| Lifestyle/Exercise | 58 |
| Metformin | 31 |
| Placebo | 0 |
Table 1.2 Intervention strategy and its effect on reducing the incidence of diabetes

### What Did We Learn?

* There is a strong association between exercise and reduced incidence of Prediabetes progressing to type II diabetes, regardless of race, gender or ethnicity.
* Metformin is effective in blood glucose management, but not as effective as exercise.
* Drug prescription isn't necessary in reducing the risk of developing type II diabetes
* Education plays a significant role in behavioural modification.

### Practical Advice

Despite no clear understanding of how exercise exerts its effect, the positive health benefits of regular moderate exercise is significant. There is substantial benefit to those not just at risk of developing diabetes, but to the community in general. Following the recommended exercise guidelines and eating habits can contribute greatly to reduced incidence of disease, particularly diabetes, and increase general health and well being.

## Further reading

Australia's Physical Activity and Sedentary Behaviour Guidelines
Cellular Mechanism of Action of Metformin
Diabetes Australia
Diabetes Prevention Program Outcome Study
Recommended Dietary Intakes for Use in Australia

### References

* 1 2 Shaw, J., & Tanamas, S. (2012). Diabetes: the silent pandemic and its impact on Australia. Diabetes Australia, Canberra. https://static.diabetesaustralia.com.au/s/fileassets/diabetes-australia/e7282521-472b-4313-b18e-be84c3d5d907.pdf
* ↑ Shaw, J. E., Sicree, R. A., & Zimmet, P. Z. (2010). Diabetes Atlas: Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Research and Clinical Practice 87(1): 4–14
* ↑ Rojas, L., B., A. and Gomes, M., B. (2013). Metformin: an old but still the best treatment for type 2 diabetes. Diabetology & Metabolic Syndrome 5, 6. DOI: 10.1186/1758-5996-5-6
* ↑ Moin T, Li J, Duru OK, Ettner S, Turk N, Keckhafer A, et al. (2015). Metformin Prescription for Insured Adults With Prediabetes From 2010 to 2012: A Retrospective Cohort Study. Ann Intern Med, 162:542-548. doi:10.7326/M14-1773
* 1 2 3 Knowler, W., C., Barrett-Connor, E., Fowler S., E., Hamman, R.,F., Lachin, J., M., Walker, E., A., Nathan, D., M.; Diabetes Prevention Program Research Group. (2002). Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. New England Journal of Medicine. 346(6): 393-403.
* ↑ Suresh, K. P. (2011). An overview of randomization techniques: An unbiased assessment of outcome in clinical research. Journal of Human Reproductive Sciences. 4(1): 8–11. doi: 10.4103/0974-1208.82352