# Exercise as it relates to Disease/Exercise and it’s ability to prevent cardiovascular events in people with type 2 diabetes

This is a critical analysis of the article “Effect of exercise intervention on endothelial function and incidence of cardiovascular disease in patients with type 2 diabetes” by Sadanori Okada, Aki Hiuge, Hisashi Makino, Ayako Nagumo, Hiroshi Takaki, Harumi Konishi, Yoichi Goto, Yasunao Yoshimasa, and Yoshihiro Miyamoto Contents

## Background

Type 2 Diabetes (T2D) is a progressive chronic condition where the body’s capacity for managing blood glucose levels and its ability to distribute it to necessary tissues is impeded. T2D is often characterized by low levels of insulin, insulin resistance and high levels of blood glucose, specifically glycated haemoglobin referred to as HbA1c. Symptoms often include, fatigue, frequent urination, thirst, weight loss, blurred vision, and poor healing. T2D often comes about because of combination of genetics and lifestyle risks such as obesity, insufficient exercise, and high energy diets. Chronic hyperglycaemia can result in severe health complications for people suffering from T2D, both on a microvascular level (i.e. nephropathies or retinopathies) and/or a macrovascular level. The macrovascular complications can include peripheral and coronary artery disease, atherosclerosis, and various other cardiovascular events. Many of these complications can result in serious debilitation or death.

## Where is the research from?

Effect of exercise intervention on endothelial function and incidence of cardiovascular disease in patients with type 2 diabetes by Okada et al was published in the Journal of Atherosclerosis and Thrombosis on the 13th of May 2010. The Journal of Atherosclerosis and Thrombosis is published via J-stage which is an online journal database and publisher that is managed by the Japanese Science and Technology agency.

## What kind of research was this?

The initial study was a randomised controlled trial (RCT) conducted over a period of three months, and there was a subsequent post hoc study that took place 24 months following randomisation. RCTs seek to reduce bias when testing the effectiveness of specific treatments, be it new or in this case when seeking further understanding of the mechanisms of prior existing treatments. Post hoc studies involve completing analyse after initial research and data collection has concluded.

## What did the research involve?

The study aimed to look at the specific role that exercise played in treating T2D. There were 38 participants (21 male, 17 female), broken into two groups, the control, and the intervention. As the study aimed to look at the role of exercise specifically, all participants in both groups received medical and dietary assistance with accord to diabetes treatment guidelines. The intervention included participants training 3-5 times a week, with each session comprising of a 10-minute warm up, 40-minutes aerobic activity, 20-minutes resistance training and a 5-minute cool down for a period of 3 months. Intensity was calculated at 60% based on the Karvonen heart formulae. The study looked at a variety of biological markers which were tested via blood test following a 12 hour overnight fast. These included: LDL, HDL, C reactive protein (CRP), HbA1c, serum adiponectin, and leptin. BMI and peak VO2 were also tested to ascertain any changes to cardiorespiratory fitness and body composition. Insulin sensitivity was determined via the steady-state plasma glucose method (SSPG), where patients receive an infusion of glucose and insulin and blood glucose is measured at 30-minute intervals for 2 hours. Endothelial function was determined via flow-mediated endothelium-dependent vasodilation (FMD), where the brachial artery diameter was measured via ultrasound and was occluded via pneumatic cuff placed around the forearm and was measured for 2-minuyes following cuff deflation. New-onset cardiovascular events were recorded in the 24-month post follow-up(1).

## What were the basic results?

In both the intervention and control there was an increase in serum adiponectin levels and HDL and there was a decrease in LDL and HbA1c. In the intervention there was a drop in BMI and increase in Peak VO2 and FMD. There was an increase in Leptin in the control group. Neither group showed any statistically significant changes within CRP levels or SSPG. Within the control group there were four cardiovascular events, with 1 case of angina pectoris and 3 cases of cerebral infarction, whilst the exercise group did not display any new cases.
Caption text :
| | Control-pre | Control-post | intervention-pre | intervention-post |
| BMI (kg/m$^2$ | 24.5 | 23.9 | 25.7 | 25.0 |
| Peak VO$_2$/kg (mL/kg/min) | 23.2 | 24.0 | 22.4 | 24.4 |
| FMD (%) | 6.4 | 7.4 | 7.3 | 10.9 |
| HbA1c (%) | 7.9 | 6.8 | 8.5 | 7.0 |
| SSPG (mmol/L) | 14.1 | 9.7 | 11.1 | 9.7 |
| HDL cholesterol (mmol/L) | 1.23 | 1.35 | 1.17 | 1.33 |
| LDL cholesterol (mmol/L) | 3.26 | 2.50 | 3.34 | 2.88 |
| Leptin (pg/mL) | 5.2 | 6.6 | 5.5 | 6.4 |
| Adiponectin (ng/mL) | 5.3 | 7.1 | 6.1 | 8.0 |
| High-sensitivity CRP (ng/mL) | 841.6 | 814.2 | 1292.6 | 1178.8 |

## What conclusions can we take from this research?

For a few of the markers (LDL, HDL, HbA1c and serum adiponectin) there was a statistically significant change in both which would suggest that these were more so influenced by a healthy diet and appropriate medication rather than any exercise intervention. The increase in peak VO2 and drop in BMI are an unsurprising result for the intervention group, as an increase in physical activity and specifically aerobic activity would likely see a positive change in body composition (i.e. loss of adipose tissue) and also improved cardio fitness. The rise in serum leptin levels for the control group is somewhat inconclusive, as leptin concentrations are strongly correlated with levels of adipose tissues, so it is difficult to discern whether this increase and the lack of change in the intervention group is related to exercise or simply the decrease in adipose tissue of the intervention group. Of note was the positive increase in FMD within the intervention group, as FMD was utilised as a surrogate marker for endothelial tissue function. This positive change could potentially explain the difference between the two groups in number of cardiovascular events, as the intervention group had 0 incidence whilst the control presented 4 in the 24 months post randomisation. Based on the training modality of the individuals within the intervention group it can not be said specifically to what degree resistance and cardio training played individually.

## Practical advice

Considering the positive change in results seen in LDL, HDL, Adiponectin, and HbA1c in both groups it is advised that individuals should eat a diet suitable for those suffering from T2D, specifically avoiding foods with a high glycaemic index such as foods high in added sugar and also saturated fats. Considering the reduction in risk of cardiovascular events and improved FMD it is highly recommended that individuals commence a suitable training program.

## Further information/resources

For further information on how to appropriately manage T2D, see the following pages.
* Diabetes Australia
* Exercise Prescription in the Treatment of Type 2 Diabetes Mellitus
* Diabtes what should I eat?
* Physical Activity/Exercise and Diabetes

## References

* 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Okada S, Hiuge A, Makino H, Nagumo A, Takaki H, Konishi H et al. Effect of Exercise Intervention on Endothelial Function and Incidence of Cardiovascular Disease in Patients with Type 2 Diabetes. Journal of Atherosclerosis and Thrombosis. 2010;17(8):828-833.
* 1 2 3 4 Blonde L. Current Antihyperglycemic Treatment Guidelines and Algorithms for Patients with Type 2 Diabetes Mellitus. The American Journal of Medicine. 2010;123(3):S12-S18.
* 1 2 3 Ramachandran A, Snehalatha C, Satyavani K, Latha E, Sasikala R, Vijay V. Prevalence of vascular complications and their risk factors in type 2 diabetes. J Assoc Physicians India. 1999;47(12):1152-1156.
* 1 2 Sut N. Study Designs in Medicine. Balkan Medical Journal. 2015;31(4):273-277.
* ↑ Reaven G, Farquhar J, Nakanishi R. Steady State Plasma Insulin Response to Continuous Glucose Infusion in Normal and Diabetic Subjects. Diabetes. 1969;18(5):273-279.
* 1 2 Alley H, Owens C, Gasper W, Grenon S. Ultrasound Assessment of Endothelial-Dependent Flow-Mediated Vasodilation of the Brachial Artery in Clinical Research. Journal of Visualized Experiments. 2014;(92).
* ↑ Zimmet P, Hodge A, Nicolson M, Staten M, de Courten M, Moore J et al. Serum leptin concentration, obesity, and insulin resistance in Western Samoans: cross sectional study. BMJ. 1996;313(7063):965-969.