Insulin Resistance

What Is Insulin Resistance?

Insulin is a hormone produced by pancreatic b-cells and plays a key role in regulating glucose homeostasis.1 Normally, pancreatic b-cells secrete insulin in response to rising levels of blood glucose. Insulin, by predominantly acting on liver, muscle, and adipose tissues, allows the body to take up, store, and use these glucose molecules as energy. Insulin resistance is the impaired biological response to insulin on these target tissues, which subsequently affects glucose homeostasis.1–3

How Is Insulin Resistance Related to Diabetes?

Although the exact mechanisms are still being elucidated, it is well understood that insulin resistance precedes the onset of clinical hyperglycemia and can be identified in virtually all patients with type 2 diabetes mellitus (T2DM).4,5

It is thought that insulin resistance develops through complex mechanisms involving nonmodifiable (eg, genetic predisposition) and modifiable risk factors (eg, obesity, physical inactivity, unhealthy diet).6,7 It is likely that persistent hyperglycemia (high blood glucose levels) and hyperlipidemia (high blood lipid levels) cause systemic inflammation and oxidative stress that lead to various genetic and biochemical defects that ultimately result in the decreased uptake and use of glucose in response to insulin (ie, insulin resistance).8,9

To compensate for this insulin resistance, pancreatic b-cells increase insulin production to maintain a normoglycemic state.6 This results in hyperinsulinemia (elevated levels of circulating endogenous insulin), a key characteristic of insulin resistance.1 However, as insulin resistance worsens over time and chronic hyperglycemia, hyperlipidemia, and hyperinsulinemia persist, b-cells undergo stress and damage, eventually leading to the disruption of proper insulin secretion.6 The resulted insulin resistance and impaired insulin secretion are often identified as key causes of T2DM.6,7

How Do I Know if I Have Insulin Resistance?

As insulin resistance is known to be related to T2DM, hypertension, dyslipidemia, cardiovascular diseases, and other comorbidities, early identification can significantly delay or prevent complications.10 Although testing for insulin resistance through the glucose clamp technique provides the most accurate result, routine use of the test is clinically impractical due to its laborious process and cost. Instead, regular screening of blood glucose levels, blood pressure, and blood lipid levels in individuals at high risk may be key to recognizing insulin resistance early on in its progression.11

How Do I Combat Insulin Resistance?

The best way to combat insulin resistance is through prevention.10,12 Making comprehensive and intensive lifestyle changes that involve physical activity, a healthy diet, and healthy weight loss has shown to be effective in preventing and delaying the onset of T2DM in high-risk individuals.13–15


  1. Moller DE, Flier JS. Insulin Resistance — Mechanisms, Syndromes, and Implications. N Engl J Med. 1991;325(13):938-948. doi:10.1056/NEJM199109263251307
  2. American Diabetes Association. Consensus Development Conference on Insulin Resistance: 5–6 November 1997. Diabetes Care. 1998;21(2):310-314. doi:10.2337/diacare.21.2.310
  3. Savage DB, Petersen KF, Shulman GI. Mechanisms of Insulin Resistance in Humans and Possible Links With Inflammation. Hypertension. 2005;45(5):828-833. doi:10.1161/01.HYP.0000163475.04421.e4
  4. Stumvoll M, Goldstein BJ, Haeften TW van. Type 2 Diabetes: Principles of Pathogenesis and Therapy. The Lancet. 2005;365(9467):1333-1346. doi:10.1016/S0140-6736(05)61032-X
  5. Taylor R. Insulin Resistance and Type 2 Diabetes. Diabetes. 2012;61(4):778-779. doi:10.2337/db12-0073
  6. Galicia-Garcia U, Benito-Vicente A, Jebari S, et al. Pathophysiology of Type 2 Diabetes Mellitus. Int J Mol Sci. 2020;21(17):6275. doi:10.3390/ijms21176275
  7. Ke C, Narayan KMV, Chan JCN, Jha P, Shah BR. Pathophysiology, Phenotypes and Management of Type 2 Diabetes Mellitus in Indian and Chinese Populations. Nat Rev Endocrinol. 2022;18(7):413-432. doi:10.1038/s41574-022-00669-4
  8. Petersen KF, Shulman GI. Pathogenesis of skeletal muscle insulin resistance in type 2 diabetes mellitus. Am J Cardiol. 2002;90(5, Supplement 1):11-18. doi:10.1016/S0002-9149(02)02554-7
  9. Solis-Herrera C, Triplitt C, Cersosimo E, DeFronzo RA. Pathogenesis of Type 2 Diabetes Mellitus. In: Feingold KR, Anawalt B, Boyce A, et al., eds. Endotext., Inc.; 2000. Accessed August 5, 2022.
  10. Rao G. Insulin Resistance Syndrome. Am Fam Physician. 2001;63(6):1159-1164.
  11. Ignacio De Artola J. Metabolic Syndrome: Early Identification and a Proactive Approach Are Warranted. Am Fam Physician. 2004;69(8):1868-1870.
  12. Kolb H, Martin S. Environmental/Lifestyle Factors in the Pathogenesis and Prevention of Type 2 Diabetes. BMC Med. 2017;15(1):131. doi:10.1186/s12916-017-0901-x
  13. Knowler WC, Barrett-Connor E, Fowler SE, et al. Reduction in the Incidence of Type 2 Diabetes with Lifestyle Intervention or Metformin. N Engl J Med. 2002;346(6):393-403. doi:10.1056/NEJMoa012512
  14. Diabetes Prevention Program Research Group, Knowler WC, Fowler SE, et al. 10-Year Follow-Up of Diabetes Incidence and Weight Loss in the Diabetes Prevention Program Outcomes Study. Lancet. 2009;374(9702):1677-1686. doi:10.1016/S0140-6736(09)61457-4
  15. Nathan DM, Barrett-Connor E, Crandall JP, et al. Long-term Effects of Lifestyle Intervention or Metformin on Diabetes Development and Microvascular Complications: the DPP Outcomes Study. Lancet Diabetes Endocrinol. 2015;3(11):866-875. doi:10.1016/S2213-8587(15)00291-0


The content of this article is intended to provide a general information and knowledge on the subject matter. The views expressed in newsletters, articles, and blogs in the i-SENS USA website are not necessarily those of i-SENS Incorporated, i-SENS USA Incorporated or our publishers. Medical or nutritional information on i-SENS USA website is not intended to replace professional medical advice – you should always consult a specialist with any questions about your specific circumstances.

Published On: August 29th, 2022 /

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