HOMA2 - %S

In part 3 of the ODX HOMA2 Series, we continue our exploration of the HOMA2 calculator by examining HOMA2-%S - an amazing way to gauge the cells' sensitivity to insulin.

HOMA2 - %S: An Index For Assessing Cellular Sensitivity to Insulin

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 sensitivity refers to the responsiveness of peripheral tissue cells to insulin and their ability to take up glucose from the bloodstream.

In patients with chronically elevated serum insulin levels, peripheral tissue cells become less sensitive to insulin and therefore require more insulin secreted by the pancreatic beta cells to take up the same amount of glucose and return serum glucose levels to normal. This is also called insulin resistance.

In patients with insulin resistance, pancreatic beta-cells respond by secreting increasing amounts of insulin to return serum glucose levels 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 HOMA2 calculator expresses the capacity of peripheral tissue cells to respond appropriately to insulin as HOMA2-%S, where a higher HOMA2-%S value indicates greater insulin responsiveness. Evidently, HOMA2-%S is directly linked to insulin resistance, as measured by HOMA2-IR; therefore, assessing HOMA2-%S without also assessing HOMA2-IR will not provide a complete picture of metabolic state. As insulin resistance increases, HOMA2-%S would decrease, and HOMA2-IR would increase.

Is there a normal 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 HOMA2-%S will be 100% in normal insulin sensitivity.

Implications of low levels focusing on the "dysfunctions" as much as the pathology 

Decreased HOMA2-%S indicates decreased insulin sensitivity in peripheral tissue cells. This is commonly seen in pre-diabetes and Type 2 Diabetes. Loss of Insulin sensitivity and decreased HOMA2-%S values are secondary to chronically elevated insulin levels, usually resulting from elevated serum glucose levels. A decreased HOMA2-%S measure would be seen in conjunction with an elevated HOMA2-IR measure, and 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. 

Is HOMA2-%S included in the Optimal DX software?

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

Research

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. [CDC Website]. 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

Up Next - HOMA2 part 4 - HOMA2 - IR: An Index For Assessing the Degree of Insulin Resistance