Homeostatic Model Assessment (HOMA)

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1 Homeostatic Model Assessment (HOMA) Historically, insulin resistance (IR) was measured with an invasive test called a euglycemic clamp test. Basically it s a test to measure how much insulin a person needs to keep their glucose level constant, despite the addition of glucose. The less insulin one requires, the more insulin sensitive one is. A much simpler way to estimate insulin sensitivity is to use a test called HOmeostasis Model Assessment (HOMA). It is a mathematical model which can estimate an individual's degree of insulin sensitivity (HOMA %S) and level of beta cell function (HOMA %B) from simultaneous measurements of fasting plasma glucose and insulin or C-peptide concentrations. (1) Types of Models Physiological Basis for HOMA Model HOMA models the physiologic glucose/insulin feedback system mathematically. It incorporates data on pancreatic beta-cell function (BCF) plus peripheral (muscle and brain) and hepatic insulin sensitivity as well as glucose and insulin measured in the fasting state. The model estimates an individual's insulin sensitivity based on the assumption that any one combination of glucose and insulin is associated with a given insulin sensitivity, or, conversely, their insulin resistance. (2) Homeostatic Model Assessment (HOMA) 1

2 HOMA1 (1985 Model) versus HOMA2 (1996 Model) In 1985, David Matthews et al published HOMA1. This model, written in Fortran, took greater account of peripheral glucose uptake and could use fasting levels of specific insulin or C-peptide in addition to RIA insulin. (3) HOMA1: The Original HOMA Model Contains a simple mathematical approximation of the original nonlinear solution to the iterative equations; the equations are widely used and simplify to: IR-Insulin resistance; FPI-Fasting plasma insulin; FPG-Fasting plasma glucose; %B-Beta cell function In 1998, Jonathan Levy et al published an updated HOMA model (HOMA2) which took account of variations in hepatic and peripheral glucose resistance, increases in the insulin secretion curve for plasma glucose concentrations above 10 mmol/l (180 mg/dl) and the contribution of circulating proinsulin. The model was recalibrated also to give %B and %S values of 100% in normal young adults when using currently available assays for insulin, specific insulin or C-peptide. (4) HOMA2: The Updated HOMA/ Computer Model Has nonlinear solutions and accounts for variations in hepatic and peripheral glucose resistance. This version incorporates an estimate of proinsulin secretion into the model and thus allows the use of either total (radioimmunoassay) or specific insulin assays. Renal glucose losses have also been included in the model, thus allowing its use in hyperglycemic subjects. HOMA2 has been recalibrated in line with current insulin assays and extended to allow the use of C-peptide if required. In 2004, the HOMA Calculator was released. This provides quick and easy access to the HOMA2 model. Validation of HOMA Model HOMA has been compared with a number of wellvalidated methods used to measure IR and BCF. Although the hyperinsulinemic euglycemic clamp and the hyperglycaemic clamp are often referred to as the gold standard tests, there is no justification for the view that these tests are yielding indexes that Homeostatic Model Assessment (HOMA) 2

3 are superior to HOMA. There is good correlation between estimates of IR derived from HOMA and from the euglycemic clamp and the minimal model. Estimates of BCF using HOMA have been shown to correlate well with estimates using continuous infusion glucose model assessment (CIGMA) (another paradigm model), hyperglycemic clamps, and the acute insulin response from the intravenous glucose tolerance test (IVGTT). Significance of HOMA Model 1. Its simplicity, reproducibility and correspondence to glucose clamp derived estimates of insulin resistance and stimulatory test estimates of insulin secretion has made HOMA a reliable and useful parameter for estimating insulin sensitivity and BCF in both, people with insulin treated (5) and non-insulin treated type 2 diabetes. (1) Clinical Significance of HOMA In diagnosis of 1. Prediabetes 2. Metabolic Syndrome 3. Therapy 2. HOMA assesses changes in BCF and IR in patients with diabetes in order to examine the natural history of diabetes and to assess the effects of treatment. For example, HOMA-IR is a useful predictor of pioglitazone treatment in type 2 diabetic patients (Araki T et al., 2005). In three different 16-week, doubleblind studies, the calculated percentage changes from baseline in insulin resistance and BCF has been summarized in the graphs below: Reduced IR & Improved BCF with Pioglitazone Therapy Compared with baseline, IR significantly decreased in pioglitazone 30 mg, sulfonylurea + pioglitazone 30 mg, and metformin + pioglitazone 30 mg treatment groups by 12.5%, 30.1%, and 18.2% respectively. Whereas, IR increased by 30.3%, 20.1% and 17.6% respectively in placebo, sulfonylurea + placebo, and metformin + placebo treatment groups. Contrarily, significant improvements in BCF was seen in pioglitazone 30 mg, sulfonylurea + pioglitazone 30 mg, and metformin + pioglitazone 30 mg treatment groups with changes of 41.4%, 38.0%, and 37.6% respectively. Compared with baseline, placebo, sulfonylurea + placebo, and metformin + placebo treatment groups also showed improvements in BCF, with changes of 23.4%, 8.2%, and 36.8% respectively. (6) 3. The Mexico City Study propounded that development of diabetes is associated with higher HOMA-IR at baseline. 4. The use of HOMA in normal populations to quantify insulin sensitivity and BCF can be helpful as it allows the collection of longitudinal data in subjects who go on to develop abnormal glucose tolerance. 5. HOMA can be used to track changes in insulin sensitivity and BCF longitudinally in individuals. The model can also be used in individuals to indicate DM=diabetes mellitus; IFG= impaired fasting glucose; IGT= Homeostatic Model Assessment (HOMA) impaired glucose tolerance; NGT= normal glucose tolerance Source: Lin KH et al. Journal of the Chinese Medical 3 Association 74 (2011)

4 whether reduced insulin sensitivity or beta-cell failure predominates. 6. The insulin-glucose-homa-model cannot be used to assess BCF in those taking exogenous insulin. Under such circumstances, the C-peptide-HOMA-model, which uses plasma C-peptide concentrations to reflect endogenous insulin secretion, could be used. (2) 7. According to Verona Diabetes Complications Study, HOMA-IR is an independent predictor of cardiovascular disease (CVD) in type 2 diabetes. The improvement of insulin resistance might have beneficial effects not only on glucose control but also on CVD in patients with type 2 diabetes. (7) Inappropriate Use of HOMA Reporting BCF in Isolation For individuals with normal glucose levels, HOMA solutions might indicate 100% BCF and 100% insulin sensitivity, or, in the case of a thin, fit individual with high sensitivity, 50% BCF and 200% insulin sensitivity. In the latter case, if the beta-cell data are reported in isolation, one might conclude erroneously that the subject had failing beta-cells, as opposed to appropriately low secretion, because the sensitivity of the body was high. A Case In September 2009, Kripa s (name changed) HOMA-IR was 1.38 (ideally it should be 1.00) one sign that she was already insulin resistant. Her fasting glucose was normal (93 mg/dl), and fasting insulin was also normal (6 mu/l). Furthermore, 2 hours after drinking 75 grams of glucose, while her glucose remained normal at 108 mg/dl, her insulin was too high, at 36 mu/l. Hence, both by HOMA- IR and insulin levels, she was clinically insulin resistant, despite never having elevated glucose levels. After making dietary alterations (restriction on sugar intake), Kripa repeated the OGTT and HOMA-IR test in May Her fasting insulin level was undetectable (less than 2 mu/l). Two hours after drinking 75 grams of glucose, her glucose went down from 97 to 83 and insulin spike was only to 16. Her HOMA-IR was now less than Both HOMA-IR and OGTT indicated that she had reversed her insulin resistance with simple dietary changes. Conclusion The HOMA model has proved to be a robust clinical tool in description of the pathophysiology of diabetes. Already quoted in more than 500 publications, it has become one of the standard tools in the armamentarium of clinicians. HOMA analysis allows assessment of inherent BCF and insulin sensitivity and can characterize the pathophysiology in those with abnormal glucose tolerance. Longitudinal data in normal subjects who go on to develop abnormal glucose tolerance is particularly informative. BCF cannot be interpreted in the absence of a measure of insulin sensitivity, and therefore HOMA %S should always be reported alongside HOMA %B. When used appropriately, HOMA can yield valuable data, but as is common with all models, the primary input data need to be robust and the data should be interpreted carefully. Homeostatic Model Assessment (HOMA) 4

5 References 1. R. Holman et al. Diabetologia 2004; 47 (1): A Wallace TM et al. Diabetes Care 2004 ; 27: Matthews DR, et al. Diabetologia 1985; 28: Levy et al. Diabetes Care 1998; 21: Okita K et al. Endocrine Journal 2013; 60 (3): Rosenstock J et al. Diabetologia 2000; 43(1): A Bonora E. Diabetes Care 2002; 25 (7): Tests Offered at SRL Test Name Method Test Code Glucose, Plasma (Fasting) Spectrophotometry 1302H Insulin, Serum (Fasting) Chemiluminescence 3192 C-peptide Chemiluminescence 3140 Homeostatic Model Assessment (HOMA) Spectrophotometry, Chemiluminescence, HOMA Calculator 7561 Register yourself at to get Updates on Recent Trends in Medical Diagnostics Homeostatic Model Assessment (HOMA) 5