Connections Between Inflammation and Insulin Resistance

IFM’s Advanced Practice Modules (APM) offer insight into a range of clinical conundrums and provide useful clinical pearls on approaching care through the functional medicine lens. Below is a question that is frequently asked by attendees during the program.

How does inflammation contribute to insulin resistance?
Over time, poor diet and lifestyle, environmental toxins, and changes in the microbiome can contribute to systemic inflammation throughout the body.1 This systemic inflammation can contribute to further metabolic dysfunctions like insulin resistance through several compounding mechanisms.

Firstly, inflammation within the skeletal muscle and adipose tissue can cause increased adiposity and risk of obesity, exacerbating the inflammatory cycle and affecting the regulation of myocyte metabolism and mitochondrial
function. 2,3 Additionally, adipose tissue also has a higher expression of insulin receptor substrate (IRS-1) and a greater ability to activate it. However, higher concentrations of inflammatory cytokines (such as TNF-α) inactivate IRS-1 which ultimately leads to impaired GLUT-4 translocation, further reducing insulin dependent transport of glucose to cells.4 The connection between inflammation, increased adipose tissue, and insulin resistance is clear. 

Specifically, increased production of inflammatory cytokines such as TNF-α, and IL-6 were shown in individuals who were overweight, and these were associated with the development of metabolic diseases.4 Consequently, the overexpression of TNF-α is positively associated with obesity, higher insulin levels, and insulin resistance.4 Additionally, newer data from 2020 has indicated that proteins like lipocalin 2 and resistin, which induce the expression of proinflammatory cytokines, have been shown to be highly expressed in individuals who are obese and have insulin resistance.4

Clinical Takeaway: Inflammation is involved in insulin resistance in several ways: inflammation increases insulin resistance by interfering with the insulin signaling pathways, and inflammation in the skeletal muscle and adipose tissue further exacerbates the inflammatory cycle. When developing a comprehensive treatment plan to support metabolic health, inflammatory triggers and mediators should always be considered.

Learn more about the role of systemic inflammation in metabolic dysfunction and how to treat patients using the functional medicine approach at the upcoming Cardio Advanced Practice Module (APM).

Learn More About Cardiometabolic Function


  1. Saad MJ, Santos A, Prada PO. Linking gut microbiota and inflammation to obesity and insulin resistance. Physiology (Bethesda). 2016; 31(4):283-93. doi: 10.1152/physiol.00041.2015.
  2. Bastard JP, Maachi M, Lagathu C, et al. Recent advances in the relationship between obesity, inflammation, and insulin resistance. Eur Cytokine Netw. 2006;17(1):4-12.
  3. Wu H, Ballantyne CM. Skeletal muscle inflammation and insulin resistance in obesity. J Clin Invest. 2017;127(1):43-54. doi: 10.1172/JCI88880.
  4. Kojta I, Chacinska M, Blachnio-Zabielska A. Obesity, bioactive lipids, and adipose tissue inflammation in insulin resistance. Nutrients. 2020;12(5):1305. doi: 10.3390/nu12051305.