Optimal - The Blog

November 8, 2020


In part 4 of the ODX HOMA2 Series we conclude our exploration of the HOMA2 calculator by examining HOMA2-IR - a powerful way to gauge the degree of insulin resistance in our patients.

HOMA2 - IR: An Index For Assessing the Degree of Insulin Resistance

Dicken Weatherby, N.D. and Beth Ellen DiLuglio, MS, RDN, LDN

The ODX HOMA2 Series

  1. HOMA2 part 1 - The HOMA2 Calculator: An Important Series of Indices for Gauging Insulin Resistance
  2. HOMA2 part 2 - HOMA2 - %B: An Index For Gauging the Beta Cell Output of Insulin from the Pancreas
  3. HOMA2 part 3 - HOMA2 - %S: An Index For Assessing Cellular Sensitivity to Insulin
  4. HOMA2 part 4 - HOMA2 - IR: An Index For Assessing the Degree of Insulin Resistance
  5. Bonus - QUICKI – An Additional Index for Assessing Insulin Resistance in Our Patients
  6. Optimal - The Podcast: Episode 5: The HOMA2 Calculator in Clinical Practice - an Interview with Dr. Brad Rachman

Insulin resistance is a term used to indicate the failure of the peripheral tissue cells to respond appropriately to insulin, therefore impairing their capacity to uptake glucose from the blood stream, and resulting in an increased serum blood glucose level. 

In patients with insulin resistance, the pancreatic beta-cells respond by secreting increasing amounts of insulin, in an effort to return serum blood glucose levels back to normal. Chronic insulin resistance is typically seen as a component of pre-diabetes, and if left untreated, will result in a decrease in beta-cell function, eventually progressing to loss of the capacity to produce and secrete insulin, and the development of T2DM. 

The HOMA 2 (Homeostasis Model Assessment) calculator is a tool used to express the degree of insulin sensitivity and insulin resistance in the patient from the following biomarkers: Fasting Blood Glucose, Fasting Insulin and/or C-Peptide.

The capacity of the peripheral tissue cells to respond to insulin appropriately is expressed by the HOMA2 calculator as HOMA2-IR, where the higher the HOMA2-IR value, the higher the level of insulin resistance. 

Evidently, the HOMA2-IR measure is directly linked to the level of insulin being secreted by the patient, as expressed by the HOMA2-%B measurement, and as such, assessment of HOMA2-IR without also assessing HOMA2-%B will not give a complete picture of metabolic state. 

Implications of High HOMA2-IR levels focusing on the "dysfunctions" as much as the pathology

Elevated HOMA2-IR is indicative of increasing levels of insulin resistance by the peripheral tissue cells. This is commonly seen in pre-diabetes and Type 2 Diabetes. Insulin resistance and elevated HOMA2-IR measures are secondary to elevated insulin levels, which is usually a result of elevated serum blood glucose levels. An elevated HOMA2-IR measure would be seen in conjunction with an elevated HOMA2-%B measurement in the pre-diabetes or perhaps early stages of Type 2 Diabetes, and would be seen in conjunction with a decreased HOMA2-%B measurement once the disease has progressed to the point of beta-cell failure. 

Implications of Low HOMA2-IR levels focusing on the "dysfunctions" as much as the pathology

Low HOMA2-IR levels are associated with reactive hypoglycemia along with a normal or decreased fasting glucose, low triglycerides, a decreased HOMA2-%B, an increased HOMA2-%s, and a decreased LDH.

A low HOMA2-IR is also associated with Pancreatogenic (Type 3c) Diabetes (T3cDM). This is a type of secondary diabetes associated with diseases of the exocrine pancreas the most common of which is chronic pancreatitis. Other diseases of exocrine pancreatitis include cystic fibrosis, pancreatic cancer, and hemochromatosis. A decreased HOMA2-IR is a sign of T3cDM along with normal or low fasting glucose, low triglycerides, and increased HOMA2-%B, a decreased HOMA2-%S, and a decreased LDH. The urine may also be positive for Urinary uric acid and urinary calcium oxalate.

Is there a standard range for HOMA2 values?

According to the Diabetes Trials Unit, the creators of the HOMA2 calculator "There is no absolute value for HOMA indices. These will depend on the specific assays used for glucose, insulin and C-peptide. Because of this, there are no defined thresholds for ‘normal’ vs. ‘abnormal’ values. Please see the following document for further details.

That being said, there is evidence that there is evidence that a normal-weight, healthy person younger than 35 years old with no insulin resistance and normal functioning beta cells will have a HOMA2-IR measurement of 1.

Is HOMA2-IR included in the Optimal DX software?

Yes! Optimal DX now gives our users the ability to add the 3 HOMA2 calculations to their patient’s Functional Health Reports.

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Many thanks to Dr. Brad Rachman of the Rachman Clinic in Black Mountain, North Carolina for your assistance in getting the HOMA2 calculator in the Optimal DX software and for your help with the ranges we are using in the software. 

Up Next - BONUS - QUICKI – An Additional Index for Assessing Insulin Resistance in Our Patients


National Diabetes Statistics Report 2017. Available at: https://www.cdc.gov/diabetes/data/statistics-report/index.html. 

National Center for Chronic Disease Prevention and Health Promotion: Diabetes.  Available at: https://www.cdc.gov/chronicdisease/resources/publications/aag/diabetes.htm. 

Wilcox G. Insulin resistance. The Clinical Biochemist Reviews [serial online]. 2005;26(2):19-39. 
Davidson MB. Counterpoint: The oral glucose tolerance test is superfluous. Diabetes Care [serial online]. 2002;25(10):1883-1885.

Wallace TM, Levy JC, Matthews DR. Use and abuse of HOMA modeling. Diabetes Care [serial online]. 2004;27(6):1487-1495.

Lorenzo C, Wagenknecht LE, Rewers MJ, Karter AJ, Bergman RN, Hanley AJ, Haffner SM. "Disposition index, glucose effectiveness, and conversion to type 2 diabetes: the Insulin Resistance Atherosclerosis Study (IRAS)". Diabetes Care. 2010;33(9):2098–103. 

Tripathy D, Almgren P, Tuomi T, Groop L. Contribution of insulin-stimulated glucose uptake and basal hepatic insulin sensitivity to surrogate measures of insulin sensitivity. Diabetes Care [serial online]. 2004;27(9):2204-2210.

Gelenoze B, Vasques ACJ, Stabe CFC, Pareja JC, de Lima Rosado LEFP, de Queiroz EC, Tambascia MA. HOMA1-IR and HOMA2-IR indexes in identifying insulin resistance and metabolic syndrome – Brazilian Metabolic Syndrome Study (BRAMS). Arquivos Brasileiros de Endocrinologia & Metabologia. 2009;53:281-287.

Susan E. Manley, Irene M. Stratton, Penelope M. Clark, and Stephen D. Luzio. Comparison of 11 Human Insulin Assays: Implications for Clinical Investigation and Research. Clinical Chemistry 2007;53:5 922–932.

Interpretation of HOMA Indices https://www.dtu.ox.ac.uk/homacalculator/HOMANoNormalRange.pdf

Tag(s): Biomarkers

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