Insulin Resistance: Definition, Factors and Causes

What is Insulin Resistance?

Insulin resistance is described as a condition in which your body is unable to respond to or use the insulin produced by the pancreas. Initially, the body compensates for the inability to process insulin by the production of even more insulin. Yet, this fails to fulfill the metabolic needs of the system and, over time, the output begins to falter, and then flounder, as the pancreas beta cells decrease in number.

By the time the disease is recognized, there are low numbers of beta cells accompanied by an oversupply of glucose in relation to utilization, more than can be handled by the available insulin. This typifies type 2 diabetes (T2D). The speed at which insulin resistance develops is slow. It begins years before you actually become diabetic. In fact, the early sign of insulin resistance, once detected, is an indicator that you will get diabetes.[1]

This decrease in the action of insulin to alter your metabolism in specific tissues applies to both naturally manufactured and artificially administered types.

Where is it Found? 

Insulin resistance takes place in the liver and other tissues, such as skeletal muscle, the primary site of glucose uptake following a meal. This contributes to the excessive rise in plasma glucose in T2D after a meal.

Factors involved in insulin resistance

Several factors are at work when determining whether you will or will not develop insulin resistance. Among them are:[2]

  • Genetics – the underlying genetic make-up will determine whether excessive glucose in comparison with energy expenditure results in T2D
  • Stress – the stress hormones may induce insulin resistance
    • Pregnancy – some pregnancies result in gestational diabetes
    • Ethnicity – this appears to play a role in who may develop insulin resistance and influences the onset of T2D
    • High blood pressure – contributes to cardiovascular disease common to diabetics
    • Abnormal levels of cholesterol and triglycerides in the blood
  • Obesity – fat interferes with insulin activity

Of these factors, one of the most studied is the link between obesity and insulin resistance.

Obesity and Insulin Resistance

An absolute and clear link between insulin resistance and obesity has not yet been established. While many obese individuals do have some resistance to insulin, not all who are obese will either develop this resistance or become diabetic. Yet, there is definitely a co-relation, although imperfect, between the degree (and type) of obesity, the presence of insulin resistance and the risk for developing T2D.

There are several factors to consider when looking at the relationship between obesity and insulin resistance. It seems to appear at a lower level body mass index (BMI) among those of Asian origins suggesting an ethnic aspect. Gender also seems to play a role. Research indicates that it has also been related to the placement of the fat on the body with specific focus being concentrated at “visceral,” intra-abdominal, fat.

Abdominal or visceral fat is located around the waist.[3] This type of fat has been discovered to metabolize in a different fashion than subcutaneous (under the skin) fat. It is also known through research that an excess of free fatty acids acts to stimulate the production of glucose in the liver. The result, over time, is a decrease in the amount of insulin released. Research indicates this applies to children of both genders as well as to both the old and the young. As a result, it is encouraged that waist circumference measurement and not strictly BMI be used to determine who may have an increased risk of developing insulin resistance and diabetes.[4]

Proposed Theories for Insulin Resistance

There are several hypotheses for the existence of insulin resistance. These include

  • Cellular activity – While it is clear that the actual mechanism for insulin resistance lies within the cells, the processes involved in its development are as yet undetermined. It is felt that the primary responsibility lies with post-receptor abnormalities e.g. impaired mitochondrial oxidation[5], decreased glucose transport. An excess of fatty acids within the liver may also impair the ability of insulin to perform. An excess storage of triglycerides in both the muscles and liver has also been found to be correlated with insulin resistance.
  • Overflow – All individuals have a limited capability to increase the quantity of fat he or she carries. If capacity is reached, any excess fatty acids overflow into other tissues. This disrupts their normal metabolic functions.
  • Defects in insulin secretion – When the blood glucose levels rise, the body responds quickly, releasing insulin as fast as it possibly can. The levels of insulin and glucose rise only to fall within a short period. The levels then rise again a few minutes later. This is termed a “double response.” It is said to arise from the availability of insulin precursors stored in the beta cells.

In an obese person, however, the beta cells do not act as they would in a person weighing a normal weight. The first response, with its immediacy, is lacking. The second response occurs but the levels are too high and it lasts for too long a period of time. The result is insulin remains for too long in the blood stream and the response is not effective. In these individuals, by the time they are diagnosed with T2DM, 50% of beta cell function has vanished. This is a predicator that therapy is a predictable failure.

Autopsy findings

In order to try to understand the progression of the disease and the evolution of insulin resistance, autopsies are performed in certain cases. The obese individual has an absolute increase in the number of beta cells. Yet, the numbers of an obese person with T2D revealed by an autopsy indicate a 50% decrease of beta cells. There is also the same decrease among non-obese persons when they have insulin resistance. It is, therefore, proposed that a decrease in beta cells is the primary factor in the reduction of insulin secretion and, as a result, contributes to the rise of insulin resistance.

Conclusion

Insulin resistance is an integral part of the route to diabetes. Its causal factors and responsible mechanisms are not known with any exactitude. While obesity and the lack of energy expenditure are linked as causal factors in both insulin resistance and the onset of T2DM, there is not an overt or exact relationship yet defined. It requires further research in order to establish the specific links between various factors, such as obesity, that are part of the journey to diabetes.

References

[1] Warshaw, HS; and Pape, J (2009). Real-Life Guide To Diabetes. Alexandria, VA: ADA.

[2] US Department of Health and Human Services (2011). “National Diabetes Information Clearing House: Insulin Resistance and Pre-diabetes.” Retrieved from http://diabetes.niddk.nih.gov/DM/pubs/insulinresistance/.

[3] Racette, SB: Evans, EM; Weiss, EP; Hagberg, JM; and Holloszy, JO (2006). “Abdominal adiposity is a stronger predictor of insulin resistance than fitness among 50–95 year olds.” Diabetes Care, 29 (3): 673–678.

[4] Parikh, RM; Joshi, SR; Menon, PS; and Shah, NS (2007).Index of Central Obesity – A Novel Parameter.” Medical Hypotheses, 68 (6): 1272-1275.

[5] Phielix, E; Szendroedi, J; and Roden, M (2011). “Mitochondrial Function and Insulin Resistance during Aging – A Mini-Review.” Gerontology, 57 (5): 387-396

This article was originally published July 12, 2012 and last revision and update of it was 9/10/2015.