Hypokinesis and Pre-Diabetes

Causes
Physiology of Insulin Resistance
Effects of Exercise

Pre-Diabetes

Pre-diabetes describes elevated blood glucose levels that are not quite high enough to be classified as diabetic.  Pre-Diabetes is characterized by insulin resistance and occurs when the cells cannot use insulin efficiently due to an insensitivity to the insulin by the cells.  The insensitivity to insulin results in high levels of insulin in the blood as well as elevated blood sugars 40.  To compensate for the high blood sugars the pancreas has to produce and secrete large amounts of insulin to keep blood sugars within normal limits.  Eventually the pancreas cannot continue this overwhelming high demand of insulin production and secretion and blood sugars elevate (hyperglycemia).  The continuation of this process leads to type 2 diabetes.  Research has shown that exercise can reverse the process of insulin resistance and prevent type 2 diabetes 50 .

Insulin Resistance
Insulin resistance is distinguished by the World Health Organization as well as other organizations for its predictive value regarding the development of type 2 diabetes 49. 

Two major subgroups can be made with individuals with insulin resistance. 65

One	Two
Typically lean	Typically overweight
Decreased beta-cell function	Typically physically inactive
Inadequate amounts of insulin produced to metabolize glucose	Insulin resistance in the muscle, liver, and adipose tissue

Group two characteristics describe those who are likely to receive the greatest benefits of exercise for reversing insulin resistance and preventing diabetes. 

Causes of insulin resistance include 44:

• Genetic abnormalities of one or more proteins of the insulin action cascade
• Fetal malnutrition
• Increases in visceral adiposity
• Decreased physical activity
• Increased counter-regulatory hormones (Coritsol)
• Pharmacologic agents

Physiology of Insulin Resistance

Insulin resistance is defined as an 8-hour fasting plasma glucose of greater than 110 but less than 126 mg/dl or as a 2-hour oral glucose tolerance test between 140-190 mg/dl 41.  Insulin resistance is a predominate characteristic that appears to proceed the development of type 2 diabetes and is associated with an increased risk of developing artherosclerosis, microvascular disease, and hypertension 41.  Insulin resistance occurs in both muscle and liver tissue and causes elevated glucose levels at rest.  At rest, an overproduction of glucose by the liver despite elevated blood insulin levels and high blood sugars represents insulin resistance in the liver 70 .  The skeletal muscle also has insulin resistance which accounts for decreased metabolism of glucose and results in high blood sugars 70. 

Fat loss and Insulin Resistance
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Increasing physical activity levels and losing excess fat weight are the keys to increasing insulin sensitivity. Both receptor and post-receptor defects are found in skeletal muscle and adipocytes 70 .  Enlarged subcutaneous abdominal fat size is associated with high blood insulin levels, insulin resistance and glucose intolerance 70 .  Abdominal obesity levels are associated with intramuscular triglyceride levels (the amount of fat stored within the muscle), which is believed to cause insulin resistance in the muscle tissue.  Since exercise reduces abdominal fat stores thereby lowering intramuscular triglyceride stores, exercise may increase insulin sensitivity 29.

Effects of Exercise on Insulin Resistance
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Insulin resistance is similar to smoking in that it is preventable and strongly predisposes to other diseases 46. Effective solutions for attaining healthy blood sugars and blood pressure levels other than taking medications are urgently needed 63. Exercise therapy is crucial considering insulin resistance caused by decreased levels of physical activity can lead to diabetes.The primary site of insulin resistance is the skeletal muscle, which uses 70-90% of the sugar metabolized during a oral glucose challenge 52.  A body composition that is high in muscle mass and low in body fat is preferable for increased insulin sensitivity given the importance of skeletal muscle in insulin stimulated glucose uptake 8.