Biomarkers of Blood Glucose Regulation: HOMA2-IR

Optimal Takeaways

Insulin sensitivity reflects the responsiveness of peripheral tissues to insulin and their ability to take up circulating glucose. Homeostatic Model Assessment (HOMA) calculations reflect peripheral resistance to insulin as well as progression to beta-cell dysfunction and diabetes. The HOMA calculations take into account glucose, insulin, and C-peptide values. Currently used HOMA calculations correlate with more invasive measures of insulin sensitivity and effectively predict progression to diabetes.

Standard Range: 0.5 - 1.75 Index

The ODX Range: 0.75 - 1.25 Index

Low HOMA2-IR may be reflective of chronic hypoglycemia and low fasting glucose.

High HOMA2-IR is associated with insulin resistance, metabolic syndrome, prediabetes, and type 2 diabetes, as well as heart failure and death (Wamil 2021). An elevated HOMA2-IR is associated with vitamin D deficiency (Dutta 2013).

Overview

HOMA calculations are used to evaluate insulin resistance, insulin sensitivity, and risk of diabetes. Updated HOMA2 calculations use fasting blood glucose, fasting insulin, and/or fasting C-peptide. The updated calculations are better at predicting progression to diabetes than the original HOMA calculations (Song 2016). The HOMA2 calculations measure insulin resistance (HOMA2-IR), beta-cell function (HOMA2-%B), and insulin sensitivity (HOMA2-%S).

HOMA2-IR assesses insulin resistance, a condition in which peripheral target tissues do not respond appropriately to insulin. As a result, blood glucose increases with a corresponding increase in insulin which, unfortunately, may continue to be ineffective. Insulin resistance leads to metabolic syndrome and type 2 diabetes.

An increasing HOMA2-IR indicates increasing insulin resistance and worsening insulin sensitivity. Healthy individuals maintain a HOMA2-IR of 1.2 (Exebio 2014), while a HOMA2-IR of 1.4 or greater identifies insulin resistance and is considered an indicator of metabolic syndrome (Mojiminiyi 2010, Demir 2020).

Evaluation of 400 adults with similar demographics defined the following cut-offs for HOMA2-IR: Below 1.22 in normal/no diabetes; 1.22-2.72 in newly diagnosed prediabetes; and above 2.72 in newly diagnosed type 2 diabetes (Elsafty 2018).

Research reveals that HOMA values even within the conventional range may be associated with type 2 diabetes (Tohid 2018, Ghasemi 2015), and HOMA2-IR values above 1.735 (at the high end of conventional) have been associated with complications such as diabetic cardiovascular autonomic neuropathy (Liu 2021). Evaluation of newly diagnosed type 2 diabetics revealed a median HOMA2-IR of 1.6 (1.1-2.2) and an increased risk of heart failure and death with increasing values (Wamil 2021).

HOMA2-IR has a strongly significant inverse correlation with serum 25(OH) vitamin D. Insulin resistance was most prevalent in prediabetics with 25(OH)D below 10 ng/mL (25 nmol/L), a level indicative of severe vitamin D deficiency (Dutta 2013).

Vitamin D supplementation significantly improved insulin resistance in a randomized, placebo-controlled, double-blind study of insulin-resistant women with vitamin D deficiency (below 20 ng/mL [50 mmol/L]). Insulin resistance improved significantly with 4,000 IU (100 ug)/day once serum 25(OH) vitamin D exceeded 32 ng/mL (80 nmol/L). Researchers note that daily supplementation with vitamin D (e.g., 4,000 IU/day) is preferable to large bolus doses (e.g., 50,000 IU weekly) that are sometimes used clinically (Von Hurst 2010).

References

Demir, Ayşe Kevser et al. “Prevalence of insulin resistance and identifying HOMA1-IR and HOMA2-IR indexes in the Middle Black Sea region of Turkey.” African health sciences vol. 20,1 (2020): 277-286. doi:10.4314/ahs.v20i1.33

Dutta, Deep et al. “Serum vitamin-D predicts insulin resistance in individuals with prediabetes.” The Indian journal of medical research vol. 138,6 (2013): 853-60.

Elsafty, Ahmed, et al. "Specific Cutoffs for HOMA1-IR, HOMA2-IR, HOMA1-% B, and HOMA2-% B in Adult Egyptian Patients." American Journal of Clinical Pathology 150.suppl_1 (2018): S66-S66.

Exebio, Joel C et al. “Use of Homeostatic Model Assessment Indexes for the Identification of Metabolic Syndrome and Insulin Resistance among Cuban-Americans: A Cross Sectional Study.” British journal of medicine and medical research vol. 4,29 (2014): 4824-4833. doi:10.9734/BJMMR/2014/8988

Ghasemi, Asghar et al. “Cut-off points of homeostasis model assessment of insulin resistance, beta-cell function, and fasting serum insulin to identify future type 2 diabetes: Tehran Lipid and Glucose Study.” Acta diabetologica vol. 52,5 (2015): 905-15. doi:10.1007/s00592-015-0730-3

Liu, Yingshan et al. “Insulin resistance is independently associated with cardiovascular autonomic neuropathy in type 2 diabetes.” Journal of diabetes investigation vol. 12,9 (2021): 1651-1662. doi:10.1111/jdi.13507

Mojiminiyi, Olusegun A, and Nabila A Abdella. “Effect of homeostasis model assessment computational method on the definition and associations of insulin resistance.” Clinical chemistry and laboratory medicine vol. 48,11 (2010): 1629-34. doi:10.1515/CCLM.2010.303

Song, Young Seok et al. “Comparison of the Usefulness of the Updated Homeostasis Model Assessment (HOMA2) with the Original HOMA1 in the Prediction of Type 2 Diabetes Mellitus in Koreans.” Diabetes & metabolism journal vol. 40,4 (2016): 318-25. doi:10.4093/dmj.2016.40.4.318

Tohidi, Maryam et al. “Fasting plasma glucose is a stronger predictor of diabetes than triglyceride-glucose index, triglycerides/high-density lipoprotein cholesterol, and homeostasis model assessment of insulin resistance: Tehran Lipid and Glucose Study.” Acta diabetologica vol. 55,10 (2018): 1067-1074. doi:10.1007/s00592-018-1195-y

von Hurst, Pamela R et al. “Vitamin D supplementation reduces insulin resistance in South Asian women living in New Zealand who are insulin resistant and vitamin D deficient - a randomised, placebo-controlled trial.” The British journal of nutrition vol. 103,4 (2010): 549-55. doi:10.1017/S0007114509992017

Wamil M, Coleman RL, Adler AI, McMurray JJV, Holman RR. Increased Risk of Incident Heart Failure and Death Is Associated With Insulin Resistance in People With Newly Diagnosed Type 2 Diabetes: UKPDS 89. Diabetes Care. 2021;44(8):1877-1884. doi:10.2337/dc21-0429