Insulin Resistance and the Effects of Exercise

Encouraging exercise, and a breakdown of insulin resistance and type 2 diabetes mellitus.

Diabetes mellitus (DM) is a disease that can be characterized by high blood sugar, secondary to deficits in the insulin response process, insulin action, or both.⁸ The presence of DM also elevates one’s risk of overall morbidity and mortality by increasing the risk of cardiovascular disease (CVD), kidney failure and other chronic metabolic health conditions.⁸

Type 2 diabetes mellitus (T2D) is a health condition mainly characterized by insulin resistance with relative insulin deficiency. It accounts for approximately 90-96% of all diabetes cases.⁸ Some risk factors for this disease include (but are not limited to):⁸

Age ≥ 45
Sedentary
BMI ≥ 25 kg/m²or central adiposity (defined by waist circumference)
Polycystic ovarian syndrome
Presence of hypertension
Presence of low level of hypodensity lipoprotein
Presence of high triglyceride level
A history of vascular disease
Other clinical conditions associated with insulin resistance

While the complete pathophysiological mechanisms of this disease are not fully known, researchers have been able to provide some insight into understanding the physiology of this condition. Under normal circumstances, following a meal, the pancreas secretes insulin which helps with the disposal of sugar out of the blood stream and into cells.

Once in the cell, glucose can then be used as energy or stored in skeletal muscle, the liver or fat cells. When insulin binds to the insulin receptors on the extracellular surface of the cell, they undergo phosphorylation. This ultimately leads towards the activation of intracellular insulin receptor substrate-1 (IRS-1). IRS-1 then upregulates phosphatidylinositol 3-kinase (Pi 3 Kinase) which helps facilitate the translocation of glucose transporter 4 (GLUT4) to the intracellular membrane. GLUT4 helps passively allow glucose to enter the cell, thus leaving the blood stream.

This insulin-dependent biochemical process aids in maintaining normal blood glucose levels. In a normal post-prandial insulin response, the amount of insulin released from the pancreas will match the amount of glucose in the blood and prevent a build-up, or hyperglycemia, of blood sugar.

In those with T2DM, insulin resistance is often the primary driving factor to the disease. Insulin resistance can be defined as a reduction in the glucose disposal rate elicited by a given insulin concentration.³ In other words, insulin cell receptors become less responsive to insulin and allow fewer insulin molecules to bind. As a result, glucose disposal is compromised, and an excess of glucose remains in the blood stream. Also, in those with T2DM, the pancreas may release less insulin than needed to help with glucose disposal.

Skeletal muscle is a primary site of glucose disposal, or uptake, under insulin stimulated conditions.⁸ While there may be a disruption in the normal functioning insulin-dependent pathway for glucose disposal, researchers have shown us there is a contraction-mediated insulin-independent pathway that also influences glucose disposal – essentially by-passing the biochemical breakdown in the insulin-dependent pathway.

Immediately after an acute bout of exercise, for example, glucose disposal in skeletal muscle is increased through an insulin-independent translocation of GLUT4 to the intracellular surface of the cell.⁷ The contraction-mediated, or insulin-independent, pathways are largely involving 5’adenosine monophosphate-activated protein kinase (5’ AMP-activated kinase) dependent and independent pathways that signal for the translocation of GLUT4 to the cell surface.⁷

As such, exercise training can help stimulate the entry of glucose into tissue and thus lowering blood glucose levels.⁶ The “Nurses’ Health Study” revealed that walking briskly for at least two and a half hours per week was associated with a 25% reduction in DM over an eight-year follow up time-frame.⁴ In a randomized clinical trial, exercise training consisting of two times per week of aerobic and resistance training reduced hemoglobin A1c (HbA_1c; average level of blood sugar over that past 2-3 months) concentrations in patients with T2DM, and improved physical fitness, systolic and diastolic blood pressure, low-density lipoprotein, and waist circumference.^1,2 Further, preliminary data suggests that yoga-based programs may provide some similar benefits to individuals with T2DM, however, no firm conclusion can be drawn at this point.⁵

It is well accepted that regular physical activity offers an effective therapeutic benefit to improve insulin action in skeletal muscle and adipose tissue in insulin resistance individuals and yields significant health benefits in patients with DM.⁸ Increased physical activity is an effective, and very well studied, intervention to not only improve insulin sensitivity and help with T2DM, but it also has an overwhelming capacity to positively influence other areas such as the immune, cardiovascular, endocrine, skeletal, muscular and respiratory systems, as well as cognitive function. The lower the fitness level, the higher the risk of developing hypokinetic-related diseases. Conversely, the higher the fitness level, the lower the risk of developing chronic diseases such as T2DM and CVD.

Like many things during this time, the fitness industry is evolving. It’s evolving in how we reach, connect, and maintain members and even how we deliver our products and experiences. While change is inevitable, we must not forget why we do what we do – we advocate and provide opportunities to live healthy and active lifestyles. We do this by encouraging and directing physical activity that, over time, improves the health, performance and overall quality of life of our members.

The importance of engaging in regular exercise will only continue to grow. As the body of evidence to support exercise is medicine continues to build, our industry will become even more appealing to help prevent and manage disease throughout the lifespan and as part of the medical/health continuum of care.

References

Balducci S, Zanuso S, Nicolucci A, et al. Effects of a intensive exercise intervention strategy on modifiable cardiovascular risk factors in subjects with type 2 diabetes mellitus; a randomized controlled trial: the Italian Diabetes and Exercise Study (IDES). Arch Int Med. 2010;170(20):1794-803.
Boule NG, Haddad E, Kenny GP, Wells GA, Sigal RJ. Effects of exercise on glycemic control and body mass in type 2 diabetes mellitus; a meta=analysis of controlled clinical trials. JAMA. 2001;286(10):1218-27
Gosland IF, and Stevension JC. Insulin resistance; syndrome or tendency? Lancet. 1995; 346(8967):100-3.
Hu FB, Sigal RJ, Rich-Edwards JW, et al. Walking compared with vigorous physical activity and risk of type 2 diabetes in women; a prospective study. JAMA. 1999;282(15):1433-39.
Innes KE, Vincent HK. The influence of yoga-based programs on risk profiles in adults with type 2 diabetes mellitus: a systematic review. Evid Based Complement Alternat Med. 2007;4(4):469-86.
Ivy JL, Zderic TW, Fogt DL. Prevention and treatment of non-insulin-dependent diabetes mellitus. Exerc. Sport Sci. Rev. 1999;130(2):89-96.
Krook A, Wallberg-Henriksson H, and Zierath J. Sending the signa: molecular mechanisms regulating glucose uptake. Med. Sci. Sports. Exerc., Vol. 36, No. 7, pp. 1212-1217, 2004.
Walter R. Thompson. ACSM’s Clinical Exercise Physiology. American College of Sports Medicine. Philadelphia: Wolers Kluwer Health, 2019.